Accepted Manuscript

Title: Manganese organometallic compounds in homogeneous

catalysis: Past, present, and prospects

Author: Dmitry A. Valyaev Guy Lavigne Noël Lugan

PII: S0010-8545(15)00220-9
DOI: http://dx.doi.org/doi:10.1016/j.ccr.2015.06.015
Reference: CCR 112102

To appear in: Coordination Chemistry Reviews

Received date: 31-3-2015

Revised date: 29-6-2015
Accepted date: 30-6-2015

Please cite this article as: <doi>http://dx.doi.org/10.1016/j.ccr.2015.06.015</doi>

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Edited June 30

Manganese organometallic compounds in homogeneous catalysis: past,

present, and prospects

Dmitry A. Valyaev,* Guy Lavigne‡ and Noël Lugan*

t
Laboratoire de Chimie de Coordination du CNRS (UPR 8241), 205 route de Narbonne, 31077

ip
Toulouse Cedex 4, France and
Université de Toulouse, UPS, INPT, 31077 Toulouse Cedex 4, France

cr
E-mail: [email protected], [email protected]
Homepage: http://www.lcc-toulouse.fr/lcc/spip.php?article24

us
‡ Deceased on April 23, 2015

Highlights
an
 Manganese is a good metal for catalysis due to its abundance and biocompatibility.
M
 Manganese organometallic complexes do catalyze a broad variety of reactions.
 Mn catalysts can provide improved chemoselectivity and functional group tolerance.
d
p te

Abstract
The use of first row transition metal complexes is one of the mainstreams in modern
ce

homogeneous catalysis. The case of manganese is peculiar in that catalytic applications of its
coordination compounds featuring nitrogen- and oxygen-based ligands are well established,
Ac

whereas those of its organometallic complexes exhibiting Mn–C and/or Mn–H bonds are still
underdeveloped and have only recently focused substantial attention. The aim of the present
report is to provide for the first time a comprehensive overview of this rapidly emerging area
and to outline some prospects.

Keywords: Organometallic manganese complexes, Cross-coupling, C–H activation,

Hydrosilylation, CO2 reduction, Electrochemical hydrogen production

Contents

1
Page 1 of 152
Edited June 30

1. Introduction
2. Mn-catalyzed cross-coupling processes
2.1. Homo- and hetero-coupling of organolithium and Grignard reagents
2.2. Cross-coupling of Grignard reagents involving carbon-halogen bond activation
2.3. Other Mn-catalyzed transformations of Grignard reagents
2.4. Cross-coupling processes leading to carbon-heteroatom bond formation

t
ip
2.5. Other types of Mn-catalyzed cross-coupling processes
3. Mn-catalyzed carbonylation reactions

cr
4. Mn-catalyzed transformations of alkenes
4.1. Alkene hydrogenation and hydroformylation

us
4.2. Mn-catalyzed reactions of alkenes with silanes
4.3. Other Mn-catalyzed alkene transformations
5. Mn-catalyzed transformations of alkynes
6.
7.
Mn-catalyzed C–H bond activation processes
Reduction of C=O double bond
an
M
7.1. Hydrosilylation of aldehydes and ketones
7.2. Hydrosilylation of carboxylic acid derivatives
7.3. Mn-catalyzed electrochemical CO2 reduction
d

8. Mn-catalyzed electrochemical hydrogen production

te

9. Mn-catalyzed dehydrogenative coupling processes via heteroatom-H bond activation

10. Miscellaneous reactions
p

Conclusion and outlook

ce

Acknowledgements
References
Ac

Abbreviations: acac, acetylacetonate; All, allyl; An, methoxyphenyl; BARF, tetrakis[3,5-

bis(trifluoromethyl)phenyl]borate; Bn, benzyl; Bu, n-butyl; Cp, η5-cyclopentadienyl; Cp’, η5-
methylcyclopentadienyl; CPE, controlled potential electrolysis; CV, cyclic voltammetry; Cy,
cyclohexyl; DCE, 1,2-dichloroethane; Dec, n-decyl; Dipp, 2,6-diisopropylphenyl; DME, 1,2-
dimethoxyethane; DMF, dimethylformamide; DMPU, 1,3-Dimethyl-3,4,5,6-tetrahydro-
2(1H)-pyrimidinone; DMSO, dimethylsulfoxide; dpm, 2,2,6,6-tetramethyl-3,5-
5
heptanedionate; Fc, ferrocene; Fp, (η -cyclopentadienyl)(dicarbonyl)iron; GC, glassy carbon;
GLC, gas-liquid chromatography; Hept, n-heptyl; Hex, n-hexyl; HMPA,
hexamethylphosphoramide; MOM, methoxymethyl; Naph, naphtyl; NMP, N-

2
Page 2 of 152
Edited June 30

methylpyrrolidone; NMO, N-methylmorpholine-N-oxide; Non, n-nonyl; Ns, p-

nitrobenzenesulfonyl; Oct, n-octyl; Pent, n-pentyl; Phen, 1,10-phenanthroline; PHMS,
polymethylhydrosiloxane; PPN, bis(triphenylphosphine)iminium; Py, pyridyl; RT, room
temperature; S/C, substrate to catalyst ratio; SET, single electron transfer; TBS, t-
butyldimethylsilyl; TEMPO, tetramethylpiperidine oxide; Tf, trifluorosulfonate; TFE, 2,2,2-
trifluoroethanol; THP, 2-tetrahydropyranyl; TMEDA, N,N,N’,N’-tetramethylethylene-

t
ip
diamine; TMP, 2,2,6,6-tetramethylpiperidine; TMS, trimethylsilyl; TOF, turnover frequency;
Tol, tolyl; TON, turnover number; Tos, p-toluenesulfonyl.

cr
1. Introduction
Catalysis plays a key role in the development of modern environmentally friendly and

us
atom-economical synthetic methods. Whereas major advances in the area of homogeneous
catalysis rest on the use of noble transition metal complexes, the search for new alternatives
based on cheap and less toxic first row transition metals has lately received considerable

an
attention from both academic and industrial chemical communities, and is becoming an
emerging trend of the 21th century. In this context, manganese is a particularly attractive
M
candidate on account of its natural abundance (the 3rd transition metal in the earth crust after
iron and titanium) and biocompatibility, which is particularly valuable for the pharmaceutical
industry. Actually, according to a recent report of the European Medicine Agency, manganese
d

and copper are considered as metals of low safety concern [1]. To date, manganese
te

coordination compounds bearing porphyrin [2], phthalocyanine [3], salen [4], or polyamine
[5] ligands have been extensively used in C–H bond oxidation and alkene epoxidation
p

processes. Though organometallic manganese complexes have received much less attention in
ce

catalysis of organic reactions, recent intense research efforts in this area are at the point to
invert such a tendency, as indicated both by the growing annual publication number and the
increase of average impact factor (Fig. 1) and by the emergence of the first outstanding
Ac

achievements in catalysis of important chemical transformations, namely direct C–H

activation processes [6-10], hydrosilylation of carbonyl compounds [11-14], electrochemical
CO2 reduction [15-21], and hydrogen generation [22-25].

3
Page 3 of 152
Edited June 30

Fig. 1. Statistical distribution of a number of original research articles dealing with the
application of manganese organometallic complexes in homogeneous catalysis multiplied by

t
ip
the annual average impact factor (for homogeneity 2013 ISI impact factors were used).

cr
The present account provides for the first time a comprehensive overview of the
applications of organometallic manganese complexes in homogeneous catalysis, covering the

us
literature up to March 2015. Its scope is limited to catalytic processes mediated by manganese
intermediates bearing Mn–C and/or Mn–H bonds. This excludes manganese-mediated
oxidative radical reactions [26] as well as alkene telomerization [27] and polymerization [28]

an
processes, which are not considered here. Several types of Mn-catalyzed reactions, namely
cross-coupling processes involving Grignard reagents [29], direct C–H bond activation [30],
M
hydrosilylation of ketones [31], and electrochemical CO2 reduction [32] have been partly
discussed in the above mentioned articles and have been presented in a recent general yet non-
exhaustive review on manganese catalysis [27].
d
te

2. Mn-catalyzed cross-coupling processes

2.1. Homo- and heterocoupling of organolithium and Grignard reagents
p

The first efficient application of manganese organometallic complexes in cross-coupling

ce

reactions rests on the pioneering work of Cahiez, Normant and coll. in 1976 [33]. These
authors reported the homo-coupling of alkenyl lithium reagents (generated in situ from
alkenyl iodides and BuLi) to give the corresponding conjugated dienes in high yield and
Ac

excellent E-selectivity (Scheme 1). The reaction is catalyzed by simple MnCl2 or MnBr2, but
for preparative purposes, the utilization of manganate complex MnCl2•2LiCl, readily soluble
in organic solvents, is preferred. The choice of ether as a solvent is crucial since more polar
solvent like THF favors an undesirable alkylation of alkenyl iodides with BuLi, even in the
absence of manganese catalyst. Among the limitations of this catalytic procedure are i) a
reduced coupling selectivity observed for the more bulky alkenyllithium CH2=C(Bu)Li
derivative, leading to the formation of 30% of alkylation product CH2=CBu2, and ii) the
impossibility to use alkenyl chloride and alkenyl bromide as coupling partners.

4
Page 4 of 152
Edited June 30

R2 R3 R 1 = H, R 2 = H, R3 = Bu 70%
R2 R3 1 2
R = Hept, R = H, R = H 3
88%
1.1 eq n-BuLi, 1% MnCl2 •2LiCl R1
 RT R1 = Et, R2 = Me, R3 =H 87%
Et2 O, -20 °C R1
R1 I
R 2 R 1 = Bu, R2 = Et, R 3 = H 91%
R3
1 2 3
R = Et, R = Bu, R = H 90%

Scheme 1. MnCl2•2LiCl-catalyzed homocoupling of alkenyllithium derivatives generated in

t
ip
situ from alkenyl iodides and BuLi [33]

cr
The proposed mechanism (Scheme 2) includes the initial formation of the trialkenyl
manganate(II) anion [1]–, which then reacts with the alkyl iodide generated in solution to

us
afford the neutral Mn(IV) intermediate 2. The later undergoes a homolytic cleavage of a Mn–
R bond to form the binuclear Mn(III) species 3 that experiences in turn a bimetallic reductive
elimination leading to the target diene and the neutral dialkenyl manganese(II) intermediate 4,

an
which can be further transformed into [1]–, thus closing a catalytic cycle. Even though a
selective reductive elimination of a diene molecule can eventually proceed, at least partially,
M
from the Mn(IV) intermediate 2, the preferred homolysis pathway is strongly supported by the
isolation of the products of alkyl radicals dimerization (R = CH2t-Bu, t-BuCH2CH2t-Bu) or
dismutation (R = n-C12H25, dodecane/1-dodecene ratio 1.3-1.7) in good yield [33].
d
te

Alkenyl I + RLi Alkenyl Li + RI

MnCl2
p

(II)
(Alkenyl) 3MnLi
ce

Alkenyl Li [1]

(II) (IV)
Ac

(Alkenyl) 2Mn (Alkenyl) 3 MnR

4 2

Alkenyl Alkenyl (III)

.
[(Alkenyl)3Mn]2 R
3

Scheme 2. Proposed mechanism for the Mn-catalyzed alkenyllithium homocoupling process

[33]

5
Page 5 of 152
Edited June 30

Some 20 years later the same research group reported the first Mn-catalyzed
homocoupling of Grignard reagents using atmospheric oxygen as an oxidant (Table 1, method
A) [34]. A broad variety of aryl-, heteroaryl-, alkenyl- and alkynyl-substituted magnesium
reagents RMgX can be efficiently coupled at RT this way, giving no more than 10% yields of
undesirable RH reduction products. The cross-coupling fails only for very electron poor (entry
34) or bulky (entry 13) aryl substrates. Importantly, several electron-withdrawing groups

t
ip
including ester, amide, cyano and nitro groups are tolerated (Table 1, entries 26-29, 31, 49),
provided the reactions are performed at low temperature, typically at –20 °C. The coupling of

cr
aryl-substituted Grignard reagents can even be realized in an intramolecular manner, as
illustrated by the synthesis of the natural product N-methylcrinasiadine (entry 31) [34]. The

us
coupling of activated alkyl Grignard reagents can be also achieved but requires a greater
catalyst loading (entry 51), or suffers from low reaction chemoselectivity (entry 54).
In 2010 Daugulis and coll. reported the application of a similar synthetic protocol to the

an
dimerization of several aryl and heteroaryl Grignard reagents generated in situ upon arene
deprotonation with the magnesium amide base TMPMgCl•LiCl (Table 1, method B, entries
M
32, 33, 37, 38, 42) [35]. For some substrates a combined action of magnesium and zinc
amides is required in order to facilitate the deprotonation step. The cheaper Cy2NMgCl•LiCl
base could be used for several substrates, albeit with a 5-10% reduced yield [35]. Importantly,
d

even electron poor and relatively bulky aryl substrates can be coupled with a reasonable
te

efficiency (entry 32 and 33).

An alternative approach for the coupling of ArMgCl reagents was concomitantly
p

developed by Zhou and coll. using DCE as oxidant (Table 1, method C) [36]. Though these
ce

cross-coupling reactions require an increased amount of manganese catalyst and typically

proceed ca. 10-15 times slower than for O2 oxidation [34, 35], the yields in biaryls products
are generally comparable. Typically, the reaction works well for nitro- (entries 28 and 30),
Ac

amino- (entries 23-24), and oxazoline-substituted (entry 25) aryl magnesium derivatives but
fails completely for heteroaryl substrates (entries 36 and 40), and provides lower yields for the
coupling of alkynyl (entry 46) and benzyl (entry 52) Grignard reagents.
Finally, a MnCl2-catalyzed dimerization of various aryl bromides can be performed
without any external oxidant using an in situ formation of the corresponding Grignard reagent
with metallic magnesium (Table 1, method D) [37]. This protocol generally leads to product
yields being 15-20% lower than those obtained via the previously discussed A-C methods,
and, as expected, fails for aryl chloride derivatives (entry 2).

6
Page 6 of 152
 Edited June 30

Table 1. MnCl2-catalyzed homocoupling of Grignard reagents [34-38]

A: 5% MnCl2 •2LiCl, dry air, RT, 45 min

[Cat] (A, B, C, or D) B: 7% MnCl2 , dry oxygen, RT, 2 h
RMgX R R
THF C: 10% MnCl2, 1.2 eq DCE, RT, 12 h
D: 10% MnCl2, 2 eq Mg, RT, 24 h

t
Entry Substrate, RMgX Cat. Product, R–R Yield Ref.

ip
1 PhMgCl Ca 99% [36]

cr
b
2 PhMgCl D 0% [37]

3 PhMgBr A 92% [34]

us
b
4 PhMgBr D 78% [37]

5 PhMgIb D 62% [37]

6
7
1-NaphMgBr
1-NaphMgBrb
C
an 89%
93%
[36]
[37]
M
D
d

8 2-NaphMgBr A 80% [34]

te

9 p-TolMgCl Ca 96% [36]

p

10 p-TolMgBrb D 75% [37]

ce

11 o-TolMgCl C 87% [36]

12 o-TolMgBrb D 55% [37]

Ac

13 MesMgBr Ac traces [38]

14 p-TMSMgBrb D TMS TMS 82% [37]

15 p-AnMgCl Ca 80% [36]

7
Page 7 of 152
 Edited June 30

16 p-AnMgBr A 95% [34]

MeO OMe
17 p-AnMgBrb D 73% [37]

18 o-AnMgCl C MeO 74% [36]

19 o-AnMgBr A 76% [34]

b

t
20 o-AnMgBr D 56% [37]
OMe

ip
21 p-MOMOC6H4MgCl Ca MOMO OMOM 58% [36]

cr
22 p-ClC6H4MgBrb D 62% [37]

us
Cl Cl

23 p-Me2NC6H4MgCl C Me2 N NMe2 54% [36]

an NMe 2
M
24 m-Me2NC6H4MgCl C 45% [36]

Me2 N
d

N N O
25 MgCl C 60% [36]
te

O O N
p

26 p-EtCO2C6H4MgCld Ae EtO2C CO2Et 80% [34]

ce

27 p-CNC6H4MgCld Ae NC CN 78% [34]

Ac

28 p-NO2C6H4MgCl C O2 N NO2 94% [36]

O 2N

29 o-NO2C6H4MgCld Ae 75% [34]

NO2

8
Page 8 of 152
 Edited June 30

NO2

MgCl
30 C 61% [36]
O 2N
O 2N

O
ClMg O

t
O

ip
N
N e
31 A 46% [34]
MgClf O
O

cr
O

F F F F CO 2Et

us
32 MgClg B 65% [35]

an
CO2Et EtO2 C F F

F F F F F
M
33 MgClg B 81% [35]

F F F F
d

F F F F
te

34 C6F5MgCl Ac F F 0% [38]
p

F F F F

35 91% [34]
ce

A
36 S MgCl C S S 0% [36]
Ac

37 Cl MgClg
B 75% [35]
S Cl S S Cl

N N S
38 MgClg B 82% [35]
S S N

39 Ae 88% [34]
EtO2 C MgCld O O
O EtO2 C CO2 Et

9
Page 9 of 152
 Edited June 30

40 2-PyMgCl C 0% [36]
N N

41 3-PyMgCl A 80% [34]

N N

t
MeO

ip
N
N N
MgClg
42 B 42% [35]
N

cr
N N
OMe
OMe

us
Bu
Bu
Bu
43 A 88% [34]
Bu
Bu MgBr
Bu

an
Ph
Ph

44 MgBr Ah 90% [34]

M
Ph
E/Z = 95:5
E/E, E/Z, Z/Z = 95:3:2
d

Hex
Hex MgBr i Hex
45 A 92% [34]
te

Z/E = 92:8 Z/Z, Z/E, E/E = 90:8:2

46 HCCMgCl 68% [36]

p

47 BuCCMgClj 91% [34]

ce

A Bu Bu

48 PhCCMgClj A Ph Ph 89% [34]

Ac

PivO PivO OPiv

49 Ah 82% [34]
MgClk

50 O N A O N N O 85% [34]
MgClk

51 BnMgCl Ak 80% [34]

52 BnMgCl C 68% [36]

53 BnMgBrb D 88% [37]

10
Page 10 of 152
 Edited June 30

Ph
Ph
25%
Ph
54 Ph MgBr A Ph 78% [34]

Ph
Ph
25% 50%
a

t
2 h reaction time

ip
b
RMgX generated in situ from RX and 2 eq of magnesium turnings
c
20% of MnCl2•2LiCl used at 0 °C

cr
d
RMgCl generated from RI and 1.1 eq of i-PrMgCl at –20 °C
e
Reaction performed at –20 °C

us
f
RMgCl generated from RI and 2.1 eq of i-PrMgCl at –25 °C
g
RMgCl generated in situ by deprotonation of the arene with 1.2-1.4 eq of TMPMgCl•LiCl
h

an
Reaction performed at 10 °C
i
Reaction performed at –40 °C
j
RMgCl generated from the terminal alkyne and 1.1 eq of i-PrMgCl at 0 °C
M
k
15% of MnCl2•2LiCl used

Though the various homocoupling processes presented above have similar outcomes,
d

they differ markedly in terms of proposed mechanisms. Indeed, in the case of oxygen-driven
te

RMgX dimerizations (methods A and B, Table 1) [34, 35] it was proposed that the incipient
neutral Mn(II) intermediate 5 transforms into the Mn(IV) peroxo complex 6, which further
p

undergoes a rapid reductive elimination (Scheme 3). The resulting peroxo Mn(II) intermediate
ce

7 would then react with two molecules of the Grignard reagent to regenerate the
organomanganese species 5, thereby completing the catalytic cycle.
Ac

11
Page 11 of 152
Edited June 30

2 RMgX + MnCl2

2 MgClX

(II) O2
XMgOOMgX
R2Mn
5

2 RMgX

t
ip
(II) O (IV) O
Mn R2 Mn

cr
7 O 6 O

us
R R

an
Scheme 3. Proposed mechanism for the oxygen-driven Mn-catalyzed homocoupling of
Grignard reagents [34]
M
In the case of aryl magnesium dimerization with DCE (method C) the authors originally
proposed that the reductive elimination takes place from the Mn(II) intermediate 5, whereas
d

the resulting Mn(0) species regenerate MnCl2 through a sequence of oxidative addition across
te

C–Cl bond in DCE, and -halogen elimination (Scheme 4a). Considering that the majority of
diaryl and dialkenyl Mn(II) compounds are stable at RT [29b] this mechanism looks rather
p

questionable to us. We propose instead that the initially formed complex 5 transforms into an
ce

anionic triaryl manganate(II) such as [9]–, which could be alkylated with DCE to form the
unstable Mn(IV) intermediate 10 (Scheme 4b). The latter could evolve similarly as complex 2
(Scheme 2), or could undergo a reductive elimination to form the biaryl and the Mn(II)
Ac

complex 11, which could be in turn transformed into 5 as described above.

12
Page 12 of 152
Edited June 30

2 RMgCl + MnCl2

2 MgCl2

2 RMgCl MgCl2 RMgCl

(II) (II)
MnCl 2 R2Mn MgCl2
2 MgCl2 RMgCl
5

(II) (II)

t
RMnCl R 3MnMgCl

ip
(II) Cl (II)
12 [9 ]
Mn R2Mn (b)
(a) DCE
8 Cl 5

cr
(II) (IV) MgCl2
RMn R 3Mn
(0) Cl

us
11 10 Cl
Mn
DCE R R
R R

an
Scheme 4. Originally proposed mechanism for the DCE-driven Mn-catalyzed homo-coupling
of Grignard reagents (a) [36] and our suggested variant (b)
M
Finally, for oxidant-free homocoupling process (method D) operating with relatively
low concentration of RMgX in the reaction mixture, the proposed reaction mechanism
d

includes an oxidative addition of the aryl bromide molecule onto the RMnCl species 11,
te

followed by a reductive elimination regenerating MnX2 (Scheme 5) [37]. Similar Mn-

catalyzed cross-coupling processes including carbon-halogen bond activation are discussed
p

below in Chapter 2.2.

ce

RMgBr
R R (II)
MnCl2
MgX2
Ac

(IV) (II)
R 2 MnX2 RMnX
13 12

RBr

13
Page 13 of 152
 Edited June 30

Scheme 5. Proposed mechanism for the Mn-catalyzed oxidant-free homocoupling of aryl

Grignard reagents [37]

The first catalytic cross-coupling of two different Grignard reagents was developed by
Cahiez and coll. in 2009 (Table 2) [38]. In contrast to the RMgX dimerization (Table 1,
method A) [34], the heterocoupling process requires an increased catalyst charge (20% vs.

t
ip
5%), lower temperature (0 °C vs. RT), and the use of pure oxygen instead of air. The
selectivity in the formation of the mixed coupling product 15 (Table 2) strongly depends on

cr
the steric and electronic properties of the coupling partners. While the coupling of bulky aryl
and alkynyl Grignard reagents is very selective and can be performed in good yields using an

us
equimolar amounts of substrates (Table 2, entries 3-4), only a 2.5 molar excess of one of the
reagents appears to be necessary to optimize the yields of the target compounds 15, since in
many cases the reaction outcome is better than expected from a simple statistical products

an
distribution [38]. Using this protocol a variety of alkynyl-(hetero)aryl (entries 1-8, 17, 18) and
aryl-(hetero)aryl (entries 9-16) products were prepared in moderate to good yield and with a
M
similar functional group tolerance. The coupling can be also readily performed for all
combinations of alkynyl and alkenyl Grignard reagents (entry 19-21) with comparable yields.
d

Table 2. MnCl2-catalyzed heterocoupling of Grignard reagents [38]

p te

20% MnCl2 . 2LiCl

ce

RMgX + 2.5 R'MgX R R + R R' + R' R'

THF, O2 , 0 °C, 1 h
14 15 16

Entry RMgX R’MgX Product, R–R’ (15) and yielda 14:15:16b

Ac

1 p-AnMgBr PentCCMgClc MeO Pent 1:4.2:3.9

72%

OMe

2 o-AnMgBr PentCCMgClc Pent

1:4.6:4.1
74%

14
Page 14 of 152
 Edited June 30

3 MesMgBr PhCCMgClc,d Ph 1:62:30

62%

Ph

t
c,d
4 1-NaphMgBr PhCCMgCl 1:7.2:0.8
72%

ip
cr
TMS
c
5 1-NaphMgBr TMSCCMgCl 1:17.8:12
89%

us
PentCCMgClc

an
6 p-ClC6H4MgBr Cl Pent 1:6.8:5.2
81%

CN
M
7 o-CNC6H4MgCle PhCCMgClc Ph
1:11:8.6
77%
d

Bu Bu
te

8 p-C6H4(MgBr)2 BuCCMgClc,f 1:7.4:6.7

74%
p

MeO
ce

9 p-AnMgBr PhMgBr 1:6.7:5

80%
Ac

p- NMe 2
10 1-NaphMgBr 1:11.3g
Me2NC6H4MgBr
68%

EtO2C OMe
11 p-EtO2CC6H4MgClh p-AnMgBr 1:12.6:14
63%

15
Page 15 of 152
 Edited June 30

OMe

12 o-AnMgBr 76%
1:5.8:4.8
S MgBr
S

CN

13 o-CNC6H4MgCle 1:10.1:8.1

t
MgBr 81%
S

ip
S

cr
14 p-AnMgBr OMe 65% 1:3.3:3.5
S MgBr
S

us
OMe
15i p-AnMgBr 1:5.9:7.4
EtO2C O MgC lk EtO2C
O
59%

16i
EtO2C O MgCl k S MgBr
an
EtO2C
O S
69% 1:8.6:7.5
M
Et 2 N
Et2N OMe
17 MgClc
p-AnMgBr 1:13:10.8
78%
d

PivO
PivO
te

18 68% 1:6.8:7
MgClc MgBr
S S
p

PivO
PivO c
19 PentCCMgCl Pent 1:10.6:10
MgClc
ce

74%

Bu Bu
PivO
20 1:16:13.4
Ac

PivO 80%
MgClc
Bu MgBr Bu

Hept
Hept 65%
MgBr
21 1:4.3:4.6
MgBr
Z/E = 94:6 Z/E = 92:8
a
Yields based on RMgX
b
Ratio based on isolated yield of compounds 14-16
c
Grignard reagent generated from the corresponding alkyne and 1.05 eq i-PrMgCl
d
1 eq of R’MgX was used

16
Page 16 of 152
 Edited June 30

e
Grignard reagent generated in situ from the corresponding bromide and 1.1 eq of i-PrMgCl•LiCl
f
5 eq of R’MgX was used
g
Yield of the corresponding product 16 was not determined in this case
h
Grignard reagent generated in situ from the corresponding iodide and 1.1 eq of Et2CHMgCl
i
Reaction carried out at –20 °C
j
Grignard reagent generated in situ from the corresponding bromide and 1.1 eq of i-PrMgCl

t
ip
2.2. Cross-coupling of Grignard reagents involving carbon–halogen bond activation

cr
In a seminal work, Cahiez, Normant and coll. reported a Mn-catalyzed reaction between
p-AnBr and BuMgCl affords the cross-coupling product in low yield, and anisole as a major

us
component (Scheme 6) [39].
2 eq BuMgCl, 1% MnCl2
MeO Br MeO Bu + MeO

an
THF, 45 °C, 16 h

20% 50%

Scheme 6. First example of Mn-catalyzed cross-coupling reaction with arylhalogenides [39]

M
Later on they showed that similar cross-coupling reactions are much more efficient
when performed on aryl halides containing electron-withdrawing groups (Scheme 7) [40].
d

Various ortho- and para-substituted aryl chlorides can be activated, whereas meta-
te

chlorobenzalimines are unreactive. The exact reaction mechanism remained unclear, yet the
authors claimed that an aromatic nucleophilic substitution is not likely implicated since aryl
p

bromide reacts with BuMgCl more rapidly than the corresponding fluoride or methoxide
ce

derivatives, and several substrates fail to react with Grignard reagents in the absence of
MnCl2.
Ac

17
Page 17 of 152
Edited June 30

Cl 1) 2 eq RMgCl, 10% MnCl2 R

Bu N THF, 0 °C or RT, 0.5-24 h R Ph o-Tol p-An Bu Cy
OHC
2) hydrolysis on SiO2 88% 62% 53% 92% 91%

Other examples:
CN
R Ph p-An Bu Cy

t
R Ph o-Tol p-An Bu Cy
OHC R R

ip
93% 46% 53% 86% 88% 77% 85% 60% 75%

Ph R

cr
Ph N
R Ph p-An 1-Naph Bu Cy
OHC
63% 93% 93% 67% 64%
O

us
32% 56%
Scheme 7. MnCl2-catalyzed cross-coupling of Grignard reagents with activated aryl halides
[40]

an
The nucleophilic aromatic substitution and Mn-catalyzed cross-coupling can be
complementary for a stepwise functionalization of diarylhalogenides with two different
M
Grignard reagents to give, after hydrolysis, 2,6-substituted benzaldehydes (Scheme 8) [40].
d

Bu Bu Bu

N N N
te

2 eq RMgCl 2 eq R'MgCl, 10% MnCl2

F Cl R Cl R R'
THF, 0 °C or RT THF, RT
p
ce

R = Bu, 90% R = Bu, R' = Ph, 83%

R = Ph, 83% R = Ph, R' = p-An, 75%

Scheme 8. Synthesis of 2,6-disubstituted benzenes using nucleophilic aromatic substitution

Ac

and Mn-catalyzed cross-coupling sequence [40]

Importantly, MnCl2-catalyzed cross-coupling with Grignard reagents can be applied

even for aromatic ortho-chloroketones (Scheme 9) [41]. Slow addition of PhMgCl at 0 °C
allows obtaining an excellent selectivity for the cross-coupling process vs. nucleophilic
addition to the ketone group, the latter becoming significant for more reactive BuMgCl.
Despite the quite limited scope of this catalytic process, these transformations can be

18
Page 18 of 152
Edited June 30

efficiently performed on a wide variety of ortho-haloketones using stoichiometric amount of

organomanganese reagents R’MnCl generated in situ [41].

Cl O R' O
R = R' = Ph 89%
R 2 eq R'MgCl, 10% MnCl2 R
R = Bu, R' = Ph 88%

t
THF, 0 °C, 3 h
R = Ph, R' = Bu 45%

ip
Scheme 9. MnCl2-catalyzed cross-coupling of Grignard reagents with ortho-chloroaryl

cr
ketones [41]

us
An elegant strategy to overcome potential chemoselectivity problems in catalytic cross-
coupling of ortho-haloketones with alkyl Grignard reagents was developed later on by Yuan

an
and coll. [42] (Scheme 10). The key feature of this protocol is a simultaneous in situ
generation of the substrate and the Grignard reagent upon acylation of dialkylmagnesium with
the corresponding benzoyl chloride at low temperature, followed by rapid MnCl2-catalyzed
M
cross-coupling. Interestingly, for alkyl Grignard reagents, the reaction typically proceeds in
higher yield for chloro-substituted derivatives, whereas for aryl analogues the use of bromo-
d

and iodo-substituted analogues is beneficial.

te

X O R O

1.3 eq R 2 Mg . LiCl, 10% MnCl2

p

Cl R
THF, -30 °C, 0.5 h
ce

X =I X = Cl

R Ph p-Tol p-An p-Me 2NC 6H 4 R Et Pr Bu Pent Hept Oct i-Pr Ph

Ac

92% 96% 88% 75% 70% 76% 93% 91% 90% 85% 81% 53%

Other examples:

O Bu O

Bu

79% 84%

Scheme 10. MnCl2-catalyzed cross-coupling of o-haloketones and Grignard reagents

generated from o-halobenzoyl chlorides and R2Mg [42]

19
Page 19 of 152
Edited June 30

A similar protocol was applied for the functionalization of various nitrogen heterocyclic
chlorides (Scheme 11) [43]. The coupling products are generally obtained in moderate to
good yields both for aromatic and aliphatic Grignard reagents using reduced catalyst loading
(1-5%). Importantly, the reaction for 4-chloroquinoline can be efficiently performed in one
pot starting from aryl bromide, magnesium and heterocyclic chloride, which is convenient

t
ip
from a practical point of view [43].
Cl R

cr
2 eq RMgCl, 1-5% MnCl2 R Ph Me Bu i-Pr i-Bu
THF, 0 °C or RT, 1.5-12 h 91% 83% 65% 89% 87%

us
N N

Other examples:

R R

N
58%
Ph Cl N N
anR N R N Ph
M
R Ph i-Pr R Ph i-Pr R Ph i-Pr R Ph i-Pr
53% 52% 71% 74% 64% 78% 82% 81%
N
R
N Ph
d

40% N
Ph N
te

N N Ph
N R N Ph
Ph N
S N N R Ph Bu R Ph i-Pr
N
p

H 84% 77% 71% 50%

47% 46% 58%
ce

Scheme 11. MnCl2-catalyzed cross-coupling of Grignard reagents with heterocyclic chlorides

[43]
Ac

Manganese-catalyzed reactions between heterocyclic iodides and Grignard reagents can

proceed in a more complex mode than a simple cross-coupling process. As a representative
example, the treatment of 2-iodobenzofurane with RMgCl in the presence of 10% MnCl2
affords, after quenching with water, o-alkenyl phenols in good yield and excellent E-
stereoselectivity (Scheme 12) [44]. Besides being hydrolyzed, the alkenyl Grignard
intermediate 17 can be trapped with different electrophiles, including PhCHO, AllBr, and
CO2.

20
Page 20 of 152
Edited June 30

R R
3 eq RMgBr, 10% MnCl2 H2 O
I
Et2 O, 0 °C  RT, 1 h MgBr
O OMgBr OH
17 R Me Et Bu All Ph
(R = Bu) 46% 88% 85% 46% 62%
Ph PhCHO AllBr CO2
Bu

t
HO

ip
Bu Bu

All

cr
OH OH O O

86% 63% 53%

Scheme 12. MnCl2-catalyzed ring opening of 2-iodobenzofuran with Grignard reagents [44]

us
The reaction is likely to proceed via the initial formation of the Mn(IV) intermediate 18
obtained by manganese/iodine exchange, followed by a reductive elimination and reaction

an
with an additional RMgX unit to give the mixed manganate(II) intermediate [19]– (Scheme
13). The latter would then undergo a ring opening with concomitant migration of alkyl (or
M
aryl) group to form the Mn(II) complex 20, which would regenerate the initial species [9]–
upon transmetallation with the excess of RMgBr.
3 RMgX + MnCl2
d

2 MgClX
te

MgX I
OMgX
17 (II)
O
R3 MnMgX
p

[9 ]
MgX2
2 RMgX
ce

R (IV)
Ac

(II) MnR 3
MnR
OMgX O 18
20

RMgX

(II)
MnR 2 MgX R R
O [19 ]

Scheme 13. Proposed mechanism for the catalytic ring opening of 2-iodobenzofuran with
Grignard reagents [44]

21
Page 21 of 152
Edited June 30

Importantly, the activation of C–I bond in 2-iodobenzofurane can proceed either by a

direct oxidative addition on the anionic manganate(II) [9]–, or via a SET from [9]– to the
heteroaryl iodide followed by recombination of heteroaryl and R3Mn• radicals. Several
catalytic processes including such SET activation of C–I bond using anionic manganate
species are discussed in detail in paragraph 2.3.
Efficient stereoselective cross-coupling reactions between conjugated chloroenynes or

t
ip
dienes and alkyl Grignard reagents were reported (Scheme 14) [45]. The use of DMPU as a
co-solvent is critical to obtain good yields and selectivity. The reaction is best performed with

cr
primary and secondary alkyl Grignard reagents, whereas using BnMgCl or bulky t-BuMgCl
results in lower product yield and reduced stereoselectivity. Various functional groups are

us
tolerated, including other types of halogens, nitrile, and unprotected alcohol. Importantly, for
the latter types of substrates, the Mn-catalyzed cross-coupling protocol is complementary to
the classic Ni- and Pd-catalyzed processes, which usually afford lower yields of coupling

an
products in the case of alkyl Grignard reagents and well operating with aryl- and alkenyl-
substituted analogues.
M
Pent 2-2.5 eq RMgCl, 3% MnCl2 . 2LiCl Pent
Cl 8 eq DMPU, THF, RT, 1.5 h R
d
R Bu Oct Bn Cy i-Pr t-Bu Ph
84% 80% 63% 95% 80% 62% 25%
te

E/Z 99:1 99:1 88:12 98:2 96:4 91:9 -

Other examples:
p

Pent Pent
R Bu Cy i-Pr t-Bu
Ph
ce

Bu Cy R 96% 89% 65% 75%

59% (E/Z 1:99) 80% (E/Z 99:1) E/Z 98:2 96:4 95:5 93:7

Pent
Ac

NC
TBSO Bu Bu Bu

78% (E/Z 99:1) 51% (E/Z 99:1) Br 88% (E/Z 99:1)

TMS Cl
Oct HO Bu R
71% (E/Z 98:2)
53% (E/Z 99:1) R = Bu, 78% (E/Z 99:1)
R = Cy, 78% (E/Z 99:1)

Scheme 14. MnCl2-catalyzed cross-coupling of Grignard reagents with conjugated alkenyl

chlorides [45]

22
Page 22 of 152
Edited June 30

The scope of this catalytic system was extended to the use of both aryl Grignard
reagents and non-activated alkenyl halides [46] (Scheme 15). The MnCl2 charge, however,
had to be increased to 10% and the presence of LiCl had to be avoided due to its detrimental
effect on the reaction rate. Actually, a variety of alkenyl bromides and alkenyl iodides can be
coupled with electron-rich aromatic Grignard reagents at RT or at 50 °C to give the products

t
ip
in good yield, whereas E-Hex(H)C=C(H)Cl reacts very slowly even upon prolonged reflux in
THF. For less reactive alkyl Grignard reagents, the reactions have to be carried out either

cr
using 20% of MnCl2 (R’ = Me, Cy), or in the presence of polar co-solvents (8 eq of DME or
TMEDA for R’ = Pr) in order to avoid side -hydride elimination processes. A complete

us
retention of the double bond configuration is observed in most cases, the stereoselectivity
being typically lower for tri-substituted alkenyl halides. Interestingly, in the case of Z-3-(2-

an
bromoethenyl)pyridine, the reaction proceed more rapidly at lower temperature (1 h at 0 °C)
affording selectively the product exhibiting inversed C=C bond configuration in 71% yield.
X R'
2 eq R'MgCl, 10% MnCl2
M
THF, RT or 50 °C, 1-18 h
R R

R = Ph,a X = Br
d
R = Hex, X = I
R' Ph p-An o-Tol p-FC 6 H 4 Me Cy R' Ph p-An 2-Naph p-Me 2NC6 H4 Pr
te

83% 81% 49% 50% 63% 73% 79% 72% 69% 61% 59%
E/Z 88:12 84:16 82:18 82:18 88:12 87:13 E/Z 99:1 98:2 96:4 99:1 -
p

Other exemples:

Ph Bu
ce

p-An p-An Ph Bu R' Et R'

65% (E/Z 96:4) 69% (E/Z 4:96) R' = Ph, 72% (E/Z 2:98) R' = Ph, 65% (E/Z 96:4)
R' = p-An, 85% (E/Z 1:99) R' = p-An, 52% (E/Z 93:7)
Ac

Pr Pr
o-An Ph Ph
t-BuO
79% (E/Z 5:95) O
Ph Ph
Ph 55% (E/Z 4:96) 75% (E/Z >1:99) 59% (E/Z 84:16)

Ph Hex Cl

N Hex Bu Ph
Ph
71% (E/Z 99:1) 75% (E/Z >1:99) 56% (E/Z 94:6) 69% (E/Z 97:3)

23
Page 23 of 152
Edited June 30

Scheme 15. MnCl2-catalyzed cross-coupling of Grignard reagents with alkenyl halides [46]
(a initial E/Z ratio 87:13)

MnCl2-catalyzed cross-coupling of Grignard reagents has been applied to several gem-

dibromocyclopropanes (Scheme 16) [44, 47]. The reaction leads to the formation of the
Grignard derivatives 21, which can be quenched with electrophiles, namely H2O or AllBr, to

t
ip
give disubstituted cyclopropanes in 47-79% yields, yet with a modest trans-selectivity. The
same reaction can be carried out with organolithium reagents, albeit with further decrease in

cr
both yield and stereoselectivity. The stereochemical reaction outcome was rationalized in
terms of the formation of the anionic manganate(II) consecutive to Mn/Br exchange from the

us
less hindered site, followed by alkyl group migration with concomitant bromide elimination
and inversion of the cyclopropane carbon atom.

an
Hex Hex Hex Hex
Br R R E
3 eq RMgBr, 10% MnCl2 +
E
+
Br THF, -78 °C  0 °C, 0.5 h MgBr E R
21
M
R = Bu, E = H 75% (cis:trans 21:79)
Other examples:
R = Bu, E = All 57% (cis:trans 19:81)
Ph H
H R = All, E = H 79% (cis:trans 42:58)
d
R = All, E = All 47%
Bu
Bu
te

51% (cis:trans 23:77) 51% (cis:trans 7:93)

p

Scheme 16. MnCl2-catalyzed cross-coupling of Grignard reagents with gem-

dibromocyclopropanes [44, 47]
ce

In case of gem-dibromoacetamide derivatives a similar cross-coupling process takes

Ac

place to produce the enolates 22 affording, after the treatment with electrophiles, the
corresponding disubstituted amides in good yield (Scheme 17) [48].

24
Page 24 of 152
Edited June 30

O OMgBr O
Br 3 eq RMgBr, 10% MnCl2 E+ E
NEt2 NEt2 NEt2
THF, -78 °C  0 °C, 0.5 h
Br R 22 R

R = Et, E = H 74%
R = Bu, E = All 61%
R = Ph, E = H 67%
Other examples:

t
ip
OH O OH O OH O

Ph NEt2 Ph NEt2 Ph NEt2

cr
Et Bu Ph
80% (syn:anti 47:53) 95% (syn:anti 45:55) 60% (syn:anti 51:49)

us
Scheme 17. MnCl2-catalyzed cross-coupling of Grignard reagents with N,N-
diethyldibromoacetamide [48]

an
By contrast, similar cross-coupling reactions with gem-alkyl dibromides lead to the
M
formation of alkene products [49]. For example, the coupling of 1,1-dibromodecane with
BuMgBr provides the corresponding E-tetradecenes in 83% yield as an equimolar mixture of
regioisomers (Scheme 18).
d

Br Pr Bu
3 eq BuMgBr, 10% MnCl2
te

Non +
THF, 0 °C  RT, 2 h
Br Non Oct
p

83% (E:Z 92:8)

ce

Scheme 18. MnCl2-catalyzed cross-coupling of Grignard reagents with 1,1-dibromodecane

[49]
Ac

The key step of the proposed catalytic cycle (Scheme 19) is a -elimination taking place
from the Mn(II) intermediate 24 to afford the alkene product and an unstable alkyl hydride
manganese complex 25. The latter decomposes to activated metallic manganese capable to
undergo the oxidative addition of dibromo alkane molecule to give the alkyl manganese
bromide 26, which in turn regenerates the starting manganate intermediate [23]– upon addition
of two molecules of Grignard reagent.

25
Page 25 of 152
Edited June 30

(II)
(RCH 2) 3MnMgX + R'CHBr2

RCH2 Br

R' (II)
MgBr2
Mn(CH 2R)2
Br

t
MgX MgX2
2 RCH2MgBr [23]

ip
cr
R' (II)
R' (II)
MnBr MnCH 2 R
Br 26 24

us
R

R'CHBr2
(0)
Mn
an (II)
RCH2 MnH
25
R'
M
R

RCH3
d

Scheme 19. Proposed catalytic cycle for the Mn-catalyzed cross-coupling of Grignard
te

reagents with 1,1-dibromoalkanes [49]

p

The selectivity of the -elimination step in this cross-coupling process can be improved
by a judicious combination of reactant and substrate. For example, the stoichiometric
ce

coupling of 1,1-dibromodecane with the bulky manganate (TMSCH2)3MnMgBr affords E-

Non(H)C=C(H)TMS only in a nearly quantitative yield. A similar approach was successfully
Ac

used in catalytic reactions involving gem-dibromo alkanes bearing a bulky OTBS group in the
-position (Scheme 20). In such cases, the reaction outcome is clearly controlled by a
chelating coordination of the oxygen moiety in the manganese intermediate 27 rendering only
one type of hydrogen atoms available for the -elimination step.

26
Page 26 of 152
Edited June 30

OTBS Pr
TBS Bu R
R Br
3 eq BuMgBr, 10% MnCl2 O Mn
THF, 0 °C  RT, 2 h
Br Bu TBSO
R

27 R = Me 60% (E/Z 92:8)

R = Ph 68% (E/Z 91:9)

t
ip
Scheme 20. Chelation-assisted Mn-catalyzed cross-coupling of BuMgBr with gem-
dibromoalkanes [49]

cr
Noticeably, this Mn-catalyzed cross-coupling is particularly effective for the

us
stereoselective synthesis of alkenylsilanes (Scheme 21) [49].

an
Br R
3 eq RMgX, 10% MnCl2 R = Me 75%
i-Pr 3Si
THF, 0 °C  RT, 2 h R = Et 88%
Br i-Pr 3Si
M
Other examples:

Bu Oct Bu R
d
Cy Ph
Si TMS TBS Si R = Bu 67%
te

Cy 95% 76% 87% Ph R = n-C16H 33 62%

p

Scheme 21. Synthesis of alkenylsilanes by MnCl2-catalyzed cross-coupling of Grignard

reagents with gem-dibromoalkanes [49]
ce

Finally, the cross-coupling of TBSCBr3 with BuMgBr leads to the formation of an

Ac

alkenyl bromide intermediate that undergoes a Mg/Br exchange under the reaction conditions
to give the vinyl Grignard product 28, affording after treatment with electrophiles, namely
H2O, AllBr, or PhCHO, alkenylsilanes in moderate yield (Scheme 22) [49].

TBS H TBS H E =H 53% (E/Z 89:11)

3 eq RMgBr, 10% MnCl 2 E+ E =D 54%
TBSCBr3
THF, 0 °C  RT, 2 h E = All 68%
BrMg Pr E Pr
E = PhCH(OH) 58%
28

27
Page 27 of 152
Edited June 30

Scheme 22. Synthesis of alkenylsilanes by MnCl2-catalyzed cross-coupling of BuMgBr with

TBSCBr3 [49]

2.3. Other Mn-catalyzed transformations of Grignard reagents

MnCl2-catalyzed cross-coupling between alkenyl triflates and Grignard reagents was
reported by Oshima and coll. (Scheme 23) [50]. Only the reactions between alkenyl triflate

t
ip
and allyl Grignard reagents proceed selectively, whereas for PhMgBr and BnMgCl, a
significant amount (15-20%) of homocoupling diene product was also observed. Vinyl and

cr
alkyl Grignard reagents react sluggishly to give the target alkenes in low yields after
prolonged reaction times (15-44 h), often accompanied by dimerization and reduction

us
byproducts.

an
Dec
Dec Dec
3 eq RMgCl, 10% MnCl2 . 2LiCl Dec
+ +
THF, 0 °C  RT, 2-5 h
OTf R
Dec
M
R Ph Bn All Me(H)C=CHCH2 CH=CH2 Me Et
Other examples:
80% 76% 92% 74% 6% 35% 24%
R
d

Pent
Pent
te

R Bn Me(H)C=CHCH2
80% 76%
p

Scheme 23. MnCl2-catalyzed cross-coupling of Grignard reagents with alkenyl triflates [50]
ce

The proposed reaction mechanism (Scheme 24) includes the formation of the Mn(IV)
Ac

intermediate 29, which undergo a reductive elimination to give either the cross-coupling
product and 5, or the alkane (arene) side products and 30. The Mn(II) species 30 obtained in
the latter case can be transformed into the bis-alkenyl Mn(IV) intermediate 32, which is the
source of the corresponding conjugated diene. A similar mixture of cross-coupling (30%) and
alkenyl homocoupling (70%) compounds was actually observed in the Mn-catalyzed
transformation of CH2=C(Bu)Li (Scheme 1) [33].

28
Page 28 of 152
Edited June 30

3 RMgX + MnCl2

2 MgClX

Alkenyl Alkenyl RMgX

(II)
R 2Mn
5

t
(IV) (II)

ip
R 2Mn(Alkenyl) 2 R 3MnMgX
32 [ 9]
MgXOTf

cr
AlkenylOTf
Alkenyl R

us
AlkenylOTf
(II) MgXOTf
R2 (Alkenyl)MnMgX (IV)
[ 31 ] R 3 Mn(Alkenyl)

an
29

(II)
RMn(Alkenyl)
M
RMgX 30
R R

Scheme 24. Proposed catalytic cycle for the Mn-catalyzed cross-coupling of Grignard
d

reagents with alkenyl triflates [50]

te

Mn-catalyzed coupling of Grignard reagents with acyl chlorides affords the

p

corresponding ketones in excellent yields and with a remarkable selectivity (Scheme 25) [51].
ce

A control of the rate of addition of the Grignard reagent led to an optimal product yield.
Worth mentioning is the excellent tolerance of this method to the presence of remote halogen,
ester, nitrile, and even ketone groups, together with the possibility to work at higher
Ac

concentrations (1.2 M vs. 0.4 M for Fe(acac)3-based system [29b]), and this is valuable in the
prospect of scaling up the synthetic procedure. Though the yields are generally ca. 20% lower
for substrates containing functional groups in close proximity to the COCl moiety, the
reaction selectivity can be restored upon addition of 3% CuCl leading to an acceleration of the
acylation. The proposed reaction mechanism is based on the acylation of the higher order
manganate R’4Mn(MgCl)4 (proceeding instantaneous even at –80 °C) followed by a reductive
elimination of ketone from the Mn(IV) intermediate, as for the previously mentioned cross-
coupling processes (Scheme 4 or 24).

29
Page 29 of 152
Edited June 30

R Bu Hept i-Pr i-Bu t-Bu

O 1.0 eq R'MgCl, 3% MnCl 2 . 2LiCl O
R' Ph Bu Hept i-Pent Hept
R Cl THF, 0 °C  10 °C, 0.5-0.75 h R R'
94% 87% 94% 83% 52%

Other examples:

t
O O O O

ip
CO2Et
Bu Et Bu Bu CO2 Et
91% 62% 83%

cr
O O
O
Br Bu CN

us
Hept Bu
79% 86% 84%

O O

an
Cl
Bu i-Pr CN
Scheme 25. Mn-catalyzed cross-coupling of Grignard reagents with acyl chlorides [51]
(a 3% of CuCl was added)
M
A synergic action of manganese and copper catalysts was also observed in the cross-
coupling of Grignard reagents with vinylic organo tellurides (Scheme 26) [52]. The reaction
d

typically proceeds with a retention of the Z-configuration, with the notable exception of the Z-
te

acrylic ester derivative, for which a complete inversion of double bond configuration was
observed.
p

O TeBu O
1.1 eq RMgBr, 5% MnCl2 , 5% CuI
ce

EtO THF, 0 °C  RT, 0.5 h EtO R

R Ph p-An p-FC 6H 4
Other examples: 78% 58% 81%
Ac

OTHP
O N Ph Ph Ph
Ph OH
52% 79% 62%
Ph R

OMe O CO2 Et
Ph Ph
78% R Ph p-An p-FC 6 H4
N N
50% 69% 54%
Ph Ph MeO N Ph Ph
45% 56% 60%

30
Page 30 of 152
Edited June 30

Scheme 26. Cross-coupling of Grignard reagents with organo tellurides [52]

The combination of manganese and copper salts is beneficial relative to copper only
catalysis in the 1,4-addition of Grignard reagents to conjugated enones (Scheme 27) [53, 54].
This has been tentatively ascribed to a Cu-catalyzed 1,4-addition of the organomanganese
species RMnCl formed in situ from RMgCl and MnCl2.

t
ip
O O
1.15 eq BuMgCl, 30% MnCl2 , 1-3% CuCl
THF, 0 °C, 1-1.5 h Bu

cr
94%
Other examples:
O
O O O O

us
Bu
Bu

Bu Bu

an
Bu
81% 93% 87% 94% 87%

Scheme 27. 1,4-addition of Grignard reagents to conjugated enones [53,54]

M
Interestingly, the reaction between alkyl Grignard reagents and cyclohexone catalyzed
by MnCl2 alone provides a mixture of 1,4-addition and reductive dimerization products
d

(Scheme 28) [55]. Though the latter procedure could be selectively applied to isophorone, all
te

attempts to extend its scope to other conjugated enones failed.

O
p

O O
ce

1.0 eq RMgCl, 5% MnCl2 . 2LiCl

+
THF, RT or lower, 0.1-1 h
R
Ac

Other example: O
R= Bu, RT 47% 45%
O R= Bu, -70 °C 85% 0%
R= i-Pr, RT 10% 62%
R= i-Pr, -90 °C 45% 16%

R = Bu, RT 77%
O

Scheme 28. MnCl2-catalyzed 1,4-addition of Grignard reagents to conjugated enones [55]

31
Page 31 of 152
Edited June 30

Manganese-catalyzed reactions between organic halogenides and Grignard reagents lead

not only to the cross-coupling or reductive substrate dimerization but also to selective
dehalogenation. In particular, the treatment of vinyl iodides with an excess of i-PrMgCl at RT
in the presence of MnCl2 leads to the formation of the corresponding alkenes in high yields
(Scheme 29) [39]. The catalytic charge could be decreased to 0.01% without any significant
alteration of the yields. The reaction was also efficient for vinyl bromides (Bu2C=C(H)Br,

t
ip
Oct(Br)=CH2, 65-94% yields) and various aryl halides, including p-AnBr, MesBr,
Me2NC6H4Br, or 1-NaphCl, albeit a gentle heating was required in the latter case.

cr
R R R H Et Bu Bu
1.5-2 eq i-PrMgCl, 1% MnCl2 . 2LiCl

us
R' Hept Bu Et Bu
I THF, RT, 3-4 h
R' R' H 93% 90% 88% 90%

an
Scheme 29. MnCl2-catalyzed dehalogenation of vinyl iodides [39]
M
The proposed reaction mechanism (Scheme 30) involves the formation of the trialkyl
manganate(II) [9]– followed by a -elimination of one or several molecules of propene to give
the hydride intermediate [33]–. The latter undergoes a Mn/halogen exchange probably via
d

SET followed by recombination of the resulting radicals with the R3Mn(III) species to give a
te

Mn(IV) hydride species 34, which can afford the final product upon reductive elimination.
p
ce
Ac

32
Page 32 of 152
Edited June 30

(II)
MnCl2 + 3 i-PrMgCl i-Pr 3MnMgCl + 2 MgCl2
[9]

n
R X
(II)
i-Pr 3-nH nMnMgCl

t
[33 ] n = 1-3

ip
MgClX

cr
(II) (IV)
i-Pr 4-nHn-1 MnMgCl i-Pr 3-nH n MnR
36 34

us
an
(II)
i-Pr 3-nH n-1Mn
i-PrMgCl R H
35
M
Scheme 30. Proposed catalytic cycle for the MnCl2-catalyzed dehalogenation of vinyl and
aryl halides [39]
d
te

The SET-dehalogenation of alkyl and aryl iodides with anionic manganate(II)

compounds can also cause an intramolecular radical cyclization to form five-membered
p

heterocycles in good yields (Scheme 31) [56]. Interestingly, the catalytic cyclizations of alkyl
ce

iodides proceed under inert atmosphere [56a], whereas for aryl iodides, the presence of a
small amount of oxygen is required for a full conversion [56b], probably to facilitate the final
-elimination step.
Ac

33
Page 33 of 152
Edited June 30

Other examples:
I
2 eq BuMgCl, 10% MnCl2 Et
THF, 0 °C, 3 h
O
O OBu
OBu
80% OBu
O
73%

t
ip
I
4 eq BuMgCl, 20% MnCl 2
air oxygen, THF, RT, 12 h

cr
O O N
70% 81%

us
Scheme 31. Mn-catalyzed dehalogenative radical cyclizations of alkyl and aryl iodides [56]

The concept of SET-induced reactions using anionic manganates was very recently used

an
in the Mn-catalyzed three-component coupling between PhMgBr, aromatic imines and THF
(Scheme 32) [57]. This protocol provides a direct access to a wide variety of 1,5-
M
aminoalcohols in good to excellent yields, yet in moderate diastereoselectivities typically
ranging from 1:1.3 to 1:4.5 (up to 1:7.5 for substrates bearing a bulky Dipp moiety).
Different sources of manganese (MnCl2, Mn(acac)2, Mn(acac)3, (CO)5MnBr, etc.) can
d

be successfully used with Mn(dpm)3 providing the best results. The presence of phenyl iodide
te

or of a radical initiator such as t-BuOOBu-t is mandatory for the reaction to occur, whereas
PhBr, alkyl iodides (BuI, i-PrI), DCE and oxygen were ineffective in that prospect. Curiously,
p

the reaction scope is restricted to imines bearing aromatic substituents on both the nitrogen
ce

and the imine carbon atoms, whereas other cyclic ethers, namely 2-methyl-THF and 1,4-
dioxane, were completely unreactive.
Ac

34
Page 34 of 152
Edited June 30

Ph NHPh
N
4.0 eq PhMgCl, 2.5% Mn(dpm) 3
OH
1.5 eq LiCl, 1.5 eq PhI, THF, RT, 18 h Ph
R
R
R H Me OMe SMe F Cl
88% 94% 97% 95% 88% 89%

t
Other examples:

ip
NHPh
R R
2-Naph OH

cr
Ph HN HN
71%
OH OH

us
NHo-Tol Et Cl Me
Ph Ph
p-An OH
R H F Cl R H Me OMe F Cl Br
Ph 51% 55% 62% 63% 74% 82% 80% 63% 70%

an
89%

NHp-An NHMes NHDipp

R OH OH OH
M
Ph Ph Ph
R R
R Ph 2-thienyl R H Cl R H F Cl
86% 94% 83% 95% 54% 62% 70%
d
te

Scheme 32. Mn-catalyzed three-component coupling between PhMgCl, imines and THF [57]
p

The coupling can be also efficiently extended to other aryl Grignard reagents (Scheme
33), but in order to suppress a competitive Mg/I exchange between RMgX and PhI potentially
ce

leading to a mixture of products, the bulky DippI activator has to be used. It is important to
note that for these substrates, the reaction often proceeds in a highly diastereoselective
Ac

manner.

35
Page 35 of 152
Edited June 30

Mes NHMes
N 5.0 eq 2-Naph MgBr, 2.5% Mn(dpm) 3 R Ph p-An
1.5 eq LiCl, 2 eq DippI, THF, RT, 18 h R OH 98% 98%
R
2-Naph

Other examples:

NHMes NHPh NHPh

t
ip
OH p-An OH OH

Cl m-Tol m-An o-Tol

MeS

cr
90% 97% 20%

NHPh NHMes NHMes

us
OH Ph OH Ph OH

MeS p-Tol

an
78% 99% 73%

NHMes NHMes Ph
M
Ph OH OH OMe
Et
2-Naph 2-Naph
82% 84%
d

Scheme 33. Mn-catalyzed three-component coupling between various aryl Grignard reagents,
te

imines and THF [57]

p

Finally, the present coupling procedure can be applied to less reactive nitrile substrates
using a higher catalyst charge of MnCl2 at 40 °C, thereby giving, after an acid hydrolysis, the
ce

corresponding 1,5-aminoketones in good to excellent yields (Scheme 34). The resulting

compounds can be directly cyclized to valuable piperidine and dihydropyran containing
Ac

compounds.

36
Page 36 of 152
Edited June 30

CN O

5.0 eq PhMgX, 10% MnCl2 , 1.5 eq LiCl, 2 eq PhI OH

THF, 40 °C, 18 h then HCl 30 °C or 50 °C, 3-5 h Ph
R
R R H SMe Ph
Other examples: 69% 56% 80%

t
O O O

ip
m-An OH OH R OH

cr
Ph R 2-Naph
67% Ph
O R m-Tol m-An R p-Tol p-An
78% 88% 85% 93%

us
N
OH

O O
91% N N

an
OH OH
R

R Ph 2-Naph
OMe
M
O 74% 94% 96%
O Ph

OH
R Ph
d

Ph Ph
R Me Ph
te

70% 53% OH 56%

Scheme 34. Mn-catalyzed three-component coupling between aryl Grignard reagents, nitriles
p

and THF [57]

ce

A proposed catalytic cycle based on joint experiments and DFT calculations is

presented in Scheme 35. The first step consists in a SET from the anionic manganate(II) [9]–
Ac

to the aryl iodide to afford an aryl radical, which abstracts a hydrogen atom from THF. A
recombination of the resulting radical with the Mn(III) species leads to the formation of the
Mn(IV) intermediate 37, subsequently converted into the anionic intermediate [38]– via a
sequence of diaryl reductive elimination and addition of the Grignard reagent. The complex
[38]– then undergoes a ring expansion with a concomitant aryl group migration to form the
Mn(II) aryl alkoxide complex [39]– that in turn undergoes the insertion of the imine molecule
to give the Mn(II) aryl amide intermediate 40. A transmetallation of the latter with two
molecules of Grignard reagent affords the final product and regenerates the initial
manganate(II) [9]–.
37
Page 37 of 152
Edited June 30

Ph
NMgCl
Ph
Ph
OMgCl
2 PhMgCl

t
Ph
(II) Ar I

ip
(II)
Ph N MnPh Ph3 MnMgCl
Ph [9]
N
.+

cr
Ph Ar MgICl
Ph
OMgCl
THF
40

us
(III)
Ph Ph3Mn
.
(II) [9 ]
.
Ar H
Mn

an
Ph O
Mg
.
Cl O

[39]
M
(IV)
Ph (II) Ph3Mn
Mn 37 O
O
Ph
d

Mg
[38] Cl
PhMgCl
te

Ph Ph

Scheme 35. Proposed catalytic cycle for the three-component Mn-catalyzed reaction between
p

aryl Grignard reagents, imines and THF [57]

ce

2.4. Cross-coupling processes leading to carbon-heteroatom bond formation

Manganese-based or manganese/copper-based catalysis can be effective for the
Ac

amination of aryl and heteroaryl halides with a broad variety of nitrogen nucleophiles (Table
3) [58-61]. Interestingly, the reactions are best performed in water while in other polar (DMF,
DMSO, THF, MeCN) or apolar (toluene) solvents yields are considerably lower. The
presence of a chelating diamine ligand is crucial for the cross-coupling process to occur either
in pure Mn-catalyzed systems (methods A and B), or in the presence of copper as co-catalyst
(methods C-E). For nucleophilic heterocyclic amines such as pyrazoles, indazole, and 7-
azaindole, the reaction can be performed using MnCl2 (method A) [58], whereas for less
nucleophilic amines and amides the catalytic system based on MnF2 provides much better
results (methods B-E) [59-61].
38
Page 38 of 152
 t
ip
Edited June 30

cr
Table 3. Mn- and Mn/Cu-catalyzed amination of aryl and heteroaryl halides [58-61]

us
an
M
ed
pt
ce
Ac

39

Page 39 of 152
 t
ip
A: 10% MnCl2 . 4H 2O, 20% L1, 2 eq K3 PO4 . H 2O, H 2O, 130 °C, 24 h
Edited June 30 R' B : 20% MnF2 , 40% L1, 2 eq Cs 2CO3, H 2 O, 130 °C, 24-48 h
R' [Cat] (A, B, C, D or E) H 2N NH 2

cr
R Hal + H N R N C: 30% MnF2 , 10% CuI, 20% L1, 2 eq KOH, H 2 O, 60 °C, 24 h L1
R'' R'' D: 30% MnF2 , 10% CuI, 20% L2, 2 eq KOH, H 2 O, 60 °C, 24 h
1.5 eq E: 10% MnF2 , 10% CuI, 20% L1, 2 eq KOH, H2 O, 60 °C, 24 h
MeHN NHMe

us
L2

Entry RHal R’R’’NH Cat. Yield Ref. Entry RHal R’R’’NH Cat. Yield Ref.

an
1 pyrrole Ca 57% [59] 12 PhCONH2 E 92% [61]
2 indole A 25% [58] 13 m-TolCONH2 E 62% [61]
a
3 indole 82% [59] 14 87% [61]

M
C p-TolCONH2 E
4 pyrazole A 78% [58] 15 p-AnCONH2 E 63% [61]
5 I pyrazole C 88% [59] 16 I p-ClC6H4CONH2 E 74% [61]

ed
6 2-Me-pyrazole A 78% [58] 17 m-FC6H4CONH2 E 47% [61]
7 indazole A 90% [58] 18 PhSO2NH2 D 83% [61]
8 indazole C 84% [59] 19 o-TolSO2NH2 D 86% [61]
pt
a
9 imidazole C 63% [59] 20 TosNH2 D 97% [61]
c
10 7-azaindole A 87% [58] 21 2-NaphSO2NH2 D 64% [61]
ce

11 7-azaindole C 93% [59] 22 2-Me-4-FC6H3SO2NH2 D 81% [61]

Br Br
Ca
Ac

23 pyrazole 71% [59]

a
25 pyrazole Ca 84% [59]
24 PhCONH2 E 77% [61]

26 pyrrole Ca 53% [59]

27 indole A 20% [58]
a
28 indole C 78% [59] 37 PhCONH2 E 45% [61]
29 pyrazole A 75% [58] 4038 PhSO2NH2 D 80% [61]
30 I pyrazole C 75% [59] 39 I o-TolSO2NH2 D 89% [61]
31 2-Me-pyrazole A 75% [58] 40 TosNH2 D 93% [61]
Page 40 of 152
32 2-Me-pyrazole C 81% [59] 41 2-NaphSO2NH2 Da 82% [61]
 t
ip
Edited June 30

cr
us
an
M
ed
pt
ce
Ac

41

Page 41 of 152
Edited June 30

In most cases, the amination reactions were carried out from aryl and heteroaryl iodides,
but aryl bromides could also be used, albeit at higher temperature (100 °C vs. 60 °C, entries
23-25, 55-57, 103-109) [59, 61]. The reaction is rather sensitive to steric factors affording low
yields of amination products for ortho-substituted aryl iodides (entries 52-54, 76-78). While

t
ip
the method A (10% MnCl2) is efficient for the amination of aryl iodides with nucleophilic
amines, an increased amount of a more active catalyst precursor (method B, 20% MnF2) is

cr
typically required for the activation of less active heterocyclic iodide substrates (entries 112-
115, 121, 123, 126) [60]. Finally, combined manganese/copper catalytic systems (methods C-

us
E) appeared to be the most efficient and universal tools, capable of performing the coupling
of both aryl and heteroaryl halides with a variety of medium and weakly nucleophilic amines,
including pyrrole, indole, or imidazole [59, 60], and even amides [61], under mild conditions.

an
Interestingly, for the amination with sulfonylamides (method D) a less bulky and more
electron-donating dimethylethylenediamine ligand (L2) has to be used instead of 1,2-trans-
M
diaminocyclohexane (L1), which is typically used in reactions with normal amides (method
E) [61]. It is also noteworthy that the presence of both MnF2 and CuI pre-catalysts is required
to perform efficiently the cross-coupling, though the origin of this synergistic effect is at
d

present not clear.

te

The amination of aryl halides with a variety of aliphatic amines (Scheme 36) has
recently been reported [62]. Aryl bromides such as PhBr, m-AnBr, and p-AnBr can be
p

coupled as well, giving similar product yields as their iodide analogues. As expected, less
ce

nucleophilic primary aliphatic amines afford lower yields than secondary ones. Contrary to
the protocols presented in Table 3 [58-61], in this case the reaction outcome is only slightly
improved in the presence of manganese catalyst (72% vs. 50% yield for non-catalyzed
Ac

reaction between PhI and morpholine). Considering the presence of a strong base and the
occurrence of mixtures of regioisomers in many cases, the reaction is likely to proceed, at
least partially, via simple aryne mechanism.

42
Page 42 of 152
Edited June 30

R R
5% MnCl2 . 4H 2 O, 10% L-proline
I + HN O N O
2 eq t-BuONa, DMSO, 135 °C, 24 h

2 eq
R H m-Me p-OMe m-Cl
Other examples:
72% 60% 70% 43%

R p-Cl p-F m-CF 3 p-CF 3

t
NHBu NHi-Pr NHi-Bu

ip
73% 56% 45% 43%

50% 40% 49%

cr
NHCy N NHBn

us
50% 80% 22%

Scheme 36. Mn-catalyzed amination of aryl iodides with aliphatic amines [62]

an
Similar MnCl2-based catalytic systems have been recently used for the thiolation of
M
vinyl- and aryl iodides (Table 4) [63, 64]. Yadavalli and coll. originally reported that a variety
of aryl and vinyl iodides can be transformed into the corresponding sulfides in good yields
using MnCl2 as catalyst along with a small amount of TMEDA as an additive (method A)
d

[63]. From bromide precursors, the corresponding sulfides were obtained in 20-25% yields
te

only. Importantly, for vinyl iodides (entries 36-43) a complete retention of the double bond
configuration was observed. Three years later, however, Lee and coll. indicated that they were
p

unable to reproduce completely their results – only 19-29% yield of diphenyl sulfide was
ce

obtained from PhI and thiophenol instead of 82% – and they rationalized this as the result of a
possible contamination of KOH used as base with catalytically active metal-containing
impurities [64]. The same group finally designed an alternative catalytic systems (methods B
Ac

and C) affording thiolation products in ca. 15-20% higher yields, even at 10 mmol scale.
Contrary to Mn-catalyzed amination reactions (Table 3) [58-61], the presence of ortho-
substituents in the starting aryl iodides leads to slight decrease of yields only (entries 14-16,
28-32, 35), and even bulky MesI can be coupled efficiently with alkylthiols (entries 26, 27)
[64].

43
Page 43 of 152
 t
ip
Edited June 30

cr
Table 4. Mn-catalyzed thiolation of vinyl and aryl iodides [63, 64]

us
A: 10% MnCl2 . 4H 2O, 1% TMEDA, 1.5 eq KOH, DMSO, 110 °C, 24 h
[Cat] ( A, B , or C)
R I + R'SH S B: 20% MnCl2, 20% Phen, 2 eq Cs2CO3, toluene 135 °C, 48 h

an
R R'
1.2 eq C: 20% MnCl2, 20% 4,7-Ph 2Phen, 2 eq Cs 2CO3 , dioxane, 135 °C, 24 h

Entry RI R’SH Cat. Yield Ref. Entry RI R’SH Cat. Yield Ref.

M
1 PhSH A 82% [63]
8 PhSH A 74% [63]
2 p-TolSH A 75% [63]
9 I PhSH B 99% [64]

ed
3 I p-AnSH A 72% [63]
10 p-AnSH B 99% [64]
4 2-NaphSH A 76% [63]
11 n-C12H25SH B 81% [64]
5 BuSH A 70% [63]
12 CySH 62% [63]
pt
A
6 PentSH A 68% [63]
13 CySH C 63% [64]
7 CySH A 65% [63]
ce

17 PhSH B 99% [64]

14 I PhSH B 91% [64] I
18 p-AnSH C 67% [64]
15 HexSH B 78% [64]
Ac

19 HexSH B 84% [64]

16 n-C12H25SH B 71% [64]
20 n-C12H25SH C 78% [64]

44

Page 44 of 152
 t
ip
Edited June 30

cr
21 PhSH A 71% [63]
I I

us
22 PhSH B 99% [64]
26 HexSH C 60% [64]
23 p-AnSH B 88% [64]
27 n-C12H25SH C 68% [64]
24 HexSH B 64% [64]

an
OMe
25 n-C12H25SH B 63% [64]

28 PhSH B 99% [64]

I

M
29 I OH p-AnSH B 89% [64]
30 p-ClC6H4SH B 76% [64] 33 PhSH A 75% [63]
31 n-C12H25SH B 82% [64]
32

I
BnSH B

ed
64% [64]

I
pt
OMe
34 PhSH A 77% [63] 35 PhSH B 80% [64]
ce

36 PhSH Aa 76% [63] I

Ac

a
37 p-AnSH A 71% [63]
I a
38 p-ClC6H4SH A 73% [63]
a
42 2-NaphSH Aa 72% [63]
39 Ph
2-NaphSH A 74% [63]
40 BuSH Aa 64% [63]
41 CySH Aa 60% [63] Ph

45

Page 45 of 152
 t
ip
Edited June 30

cr
I

us
43 PhSH Aa 72% [63] 44 EtO2 C I
PhSH Aa 0% [63]

an
F

a
15 h reaction time

M
ed
pt
ce
Ac

46

Page 46 of 152
Edited June 30

2.5. Other types of Mn-catalyzed cross-coupling processes

MnBr2 alone can replace copper and palladium traditionally used in Stille coupling
(Table 5) [65]. The reaction is performed at high temperature in strongly polar solvents such
as NMP or DMF, and upon slow addition of the stannane to avoid the homocoupling of the
latter. Interestingly, MnBr2 is superior to MnCl2•4H2O giving lower yield of cross-coupling

t
ip
products, and especially to MnI2, which is completely inactive. The addition of chloride salt
exhibiting non-coordinating cations such as Na+ or K+ is crucial to ensure high reaction yield

cr
and selectivity. Other additives such as LiCl, KF, or CsF promote the homocoupling of the
stannanes. Under optimized reaction conditions, a variety of aryl, heteroaryl, vinyl, and

us
alkynyl stannanes can thus be coupled with aryl and vinyl iodides in good to excellent yield.
While the coupling always proceeds stereoselectively for E-Ph(H)=C(H)I, the application of
this protocol to its Z-isomer provides a 1:1.4 mixture of the corresponding E,Z- and E,E-
conjugated dienes in 86% combined yield.

an
M
Table 5. Mn-catalyzed Stille coupling [65]
d

10% MnBr 2, 1 eq NaCl

R SnBu 3 + R I R R'
NMP, 120 °C, 6-16 h
te

Entry RSnBu3 PhI p-C6H4I2

p

p-TolI p-AnI
Ph
ce

1 SnBu3 - 76% 85%a - 72%

Ac

2 92%b - 86%b 80%c 75%

S SnBu 3

3 - - 90%a - 80%b
O SnBu 3

4 SnBu3
- - - - 70%b

SnBu3
5 80% - - - 81%
Ph

47
Page 47 of 152
Edited June 30

Ph SnBu 3
6 88%b - - - 71%
a
Reaction carried out at 90 °C
b
Reaction carried out at 100 °C
c
Reaction carried out at 110 °C

t
ip
The homocoupling of various organostannanes can be performed selectively under
similar reaction conditions using 0.5 eq of iodine (Scheme 37) [66]. By contrast to the

cr
previous protocol no salt additives are necessary for optimal catalytic performances.

us
10% MnBr 2, 0.5 eq I2 R Ph p-An
R SnBu 3 R R
NMP, 100 °C, 5 h 70% 85%

an
Other examples:

Ph
Ph 90%
M
O O S S
80% 83% Ph Ph 81%
d

Scheme 37. Mn-catalyzed homocoupling of organostannanes [66]

te

Mn-catalyzed cross-coupling of organostannanes with iodonium salts to afford biaryls

p

has been reported (Scheme 38) [67]. In the case of non-symmetrical iodonium salts, alkenyl,
alkynyl, and more electron-rich aryl fragments are incorporated selectively into the coupling
ce

product. Here, MnCl2•4H2O act as a suitable catalytic precursor, whereas MnBr2 is

completely inactive. The reaction is best carried out in THF/NMP mixtures being less
Ac

efficient in each of these pure solvents.

R Ph 2-furyl 2-furyl 2-thienyl 2-thienyl

5% MnCl2 . 4H2O
R SnBu 3 + R' I R R'
Ph R' Ph Ph p-An Ph p-An
THF/NMP, 70 °C, 15 h
72% 84% 61% 80% 54%
BF4
Other examples:

Ph Ph Ph
Ph Ph
O S Ph

47% 48% 67% 72%

48
Page 48 of 152
Edited June 30

Scheme 38. Mn-catalyzed cross-coupling of organostannanes with aryliodonium salts [67]

A synthetically useful protocol for the preparation of alkylzinc bromide compounds

from Et2Zn and primary alkyl bromides was developed by Knochel, Cahiez and coll. using a
mixed Mn/Cu-based catalytic system in highly polar DMPU solvent (Scheme 39) [68]. It is
noteworthy that in contrast to alkyl iodide derivatives, alkyl bromides typically react very

t
ip
sluggishly with a zinc dust, even in the presence of copper salts. Here, organozinc bromides
bearing various important functional groups such as chloride, ester, or nitrile can be obtained

cr
in ca. 80-85% yield under mild conditions, and further quenched with electrophiles, or used in
Pd cross-coupling or Cu-catalyzed 1,4-addition to unsaturated ketones [68].

us
5% MnBr 2 , 3% CuCl
OctBr + Et2Zn OctZnBr
DMPU, RT, 4-10 h

an
85%

Other examples:

Cl
M
EtO2C ZnBr NC ZnBr ZnBr

Scheme 39. Mn/Cu-catalyzed transmetallation of alkyl bromides with diethylzinc [68]

d

These organozinc reagents can also be generated under Barbier conditions at 60 °C from
te

the corresponding bromo- or iodo-substituted aldehydes or ketones to give in fine mono-, bi-
and spiro-cyclic alcohols in good yields and excellent stereoselectivities (Scheme 40) [69,
p

70].
ce

O R Other examples:
Br
Ac

R OH OH
HO
5% MnBr 2, 3% CuCl CO2 Et
+ Et2Zn
DMPU, 60 °C, 0.5-3 h
Bu
82% 83%
R H Bu (CH 2) 3OAc d.r. > 95:5
95% 72% 73%

Scheme 40. Mn/Cu-catalyzed generation of alkylzinc bromides under Barbier conditions [69,
70]

49
Page 49 of 152
Edited June 30

The reaction mechanism remains unclear and possibly includes several

transmetallations. Yet, a strong evidence for the involvement of alkyl radical species was
obtained for substrates bearing a pendant alkene moiety (Scheme 41) [69]. These radical
cyclizations are highly stereoselective allowing to control up to three contiguous stereocenters
in the corresponding organozinc compounds 41, which could be quenched by electrophiles
(H2O, I2), or directly used for Cu-catalyzed 1,4-addition to α,-unsaturated esters, or Pd-

t
ip
catalyzed cross-coupling.

cr
H
H
Br ZnBr
5% MnBr 2 , 3% CuCl

us
+ Et2Zn R
DMPU, 60 °C, 12 h O
O O R 1.1 eq O
H 41

an
Scheme 41. Mn/Cu-catalyzed radical cyclization of alkyl bromides with pendent alkene
moiety using diethylzinc [69]
M
3. Mn-catalyzed carbonylation reactions
In 1965, Calderazzo reported a Mn-catalyzed transformation of amines into the
d

corresponding ureas and hydrogen at high temperature and high CO pressure (Scheme 42)
te

[71]. Both carbonyl-containing pre-catalysts, namely Mn2(CO)10 and (CO)5MnMe, are

equally effective in heptane, showing TON of 94 and 102, respectively, whereas inorganic
p

manganese(II) compounds such as Mn(OAc)2 show no activity at all. The reaction is

ce

relatively efficient for primary alkylamines, affording only small amounts of N-substituted
formamides in the case of ammonia, aniline, or secondary alkylamines.
Ac

0.45% of Mn 2(CO) 10 or 0.25% (CO) 5MnMe RHN NHR

2 RNH2 + CO + H2
heptane or THF, 135 atm CO, 180-200 °C, 12 h
O

R = Bu 47% (heptane), 52% (THF)

Mn2 (CO) 10
R = Cy 41% (heptane), 58% (THF)
R = Bu 33% (THF)
(CO) 5 MnMe
R = Cy 25% (heptane)

Scheme 42. Mn-catalyzed dehydrogenative carbonylation of primary alkylamines [71]

50
Page 50 of 152
Edited June 30

Selective homologation of methanol with syngas is catalyzed by Mn2(CO)10 providing

ethanol and small amount of methane (Scheme 43) [72-75]. The reaction proceeds only in the
presence of bases such as tertiary amines [72, 73, 75] or potassium formate [74], and can be
accelerated upon addition of MeI or PBu3. Lower selectivity is observed in the case of
potassium formate affording acetaldehyde, its acetals, and ethylformate as side products.
Whereas a Fe(CO)5-catalyzed process afforded more methane (TOF 0.75 h–1) than ethanol

t
ip
(0.35 h–1), the use of a mixed Mn/Fe catalytic system and diamine 43 is highly beneficial to
the ethanol production rate.

cr
0.33% Mn 2 (CO)10 , additive, base

us
CH3 OH CH3 CH2 OH + CH 4 + CO2
300 atm CO/H2 3:1, 200 °C, 6 h

TOF a EtOH, h-1 TOF a CH 4, h-1 N

an
additive base
none 2M soln. of 42 0.75 0.15
2% MeI 2M soln. of 42 2.15 0.35
42
1.5% PBu3 2M soln. of 42 2.4 0.25
M
4.5% Fe(CO) 5 2M soln. of 42 2.4 0.5
33% Fe(CO) 5 2M soln. of 42 3.6 0.6 N N
43
33% Fe(CO) 5 1.65M soln. of 43 7.9 b 3.1 b
d
te

a
The TOF values were calculated based on the mononuclear complex (CO) 5 Mn
b The reaction was carried out at 220 °C for 2 h
p

Scheme 43. Mn-catalyzed homologation of methanol with syngas [72-75]

ce

The proposed catalytic cycle based on experimental data and reaction kinetics studies is
summarized in Scheme 44. Manganese carbonyl is first transformed into the hydride complex
Ac

44, which is subsequently deprotonated to give the anionic manganate [45]– being the actual
active species. In parallel, methylformate formed in situ from MeOH and CO reacts with the
tertiary amine to give the formate anion and the quaternary ammonium salt [48]+. The latter
reacts with [45]– to afford the σ-methyl complex 46, which undergoes either a carbonylation
to give the σ-acyl complex 47 (major path), or reaction with hydrogen to give methane (minor
path). Finally, the complex 47 reacts with hydrogen to afford the initial manganese hydride 44
and acetaldehyde, further catalytically reduced into ethanol under the reaction conditions. The
remarkable selectivity of a methanol vs. ethanol homologation using this catalytic system was
referred to the easier SN2 substitution between a methylformate and amine molecule than in
51
Page 51 of 152
Edited June 30

case of ethylformate. The beneficial effect of iron carbonyl was mainly attributed to the
acceleration of formate anion decomposition step.

Mn 2(CO) 10 H2 + CO2
H2
[H] R 3N
EtOH MeCHO

t
ip
(CO) 5MnH
44 MeOH + CO
H2 R3NH HCO2

cr
CH4 R 3N
(CO) 5 MnCOMe (CO) 5Mn HCO2Me

us
47 [45]
H2
R 3NMe

an
[48 ] +

(CO) 5MnMe
CO 46 R 3N
M
Scheme 44. Proposed catalytic cycle for the Mn-catalyzed homologation of methanol with
syngas [72-75]
d
te

Mn-catalyzed cross-coupling of organostannanes with iodonium salts under a CO

atmosphere leads to the formation of ketone products (Scheme 45) [67]. Here, a competitive
p

transfer of alkenyl and aryl groups from the non-symmetrical iodonium salt takes place to
ce

give a ca. 2:1 mixture of target products. This is in sharp contrast with the earlier case of non-
carbonylative cross-coupling (Scheme 38), where a selective transfer of the alkenyl moiety
was observed. However, reaction of the symmetrical Ph2IBF4 salt with the same heterocyclic
Ac

stannanes afforded the 2-furyl and 2-tienylphenyl ketones in 81 and 82% yield, respectively.

5% MnCl2 . 4H 2O, 1 atm CO Ph Ph

SnBu 3 +
X THF/NMP, 60 °C, 15 h X X
O O
+
I 51% X=O 28%
Ph Ph 43% X= S 25%
BF4

52
Page 52 of 152
Edited June 30

Scheme 45. Mn-catalyzed carbonylative cross-coupling between heterocyclic stannanes and

iodonium salts [67]

A Mn-based carbonylation of alkyl iodides in the presence of methanol to give the

corresponding esters was first reported by Watanabe and coll. (Scheme 46) [76, 77]. The
(CO)5MnK catalyst could be either used as such, or generated in situ upon electrochemical

t
ip
reduction of Mn2(CO)10, both variants being equally efficient. Very characteristically, the
nature of the cation has a marked influence on the product yield, as illustrated by the

cr
carbonylation of CyI, where the yields in ester obtained with 4% of PPN, Li, Na, and K salts
used as catalysts were 23%, 68%, 84% and 73%, respectively.

us
OMe
2% (CO)5MnK, 1 atm CO, 6 eq MeOH R Cy 2-Oct t-Bu
R I R

an
0.6 eq K2CO3, THF, RT, 6-24 h 62% 37% 35%
O

Scheme 46. Mn-catalyzed carbonylation of alkyl iodides in the presence of methanol [76]
M
The proposed mechanism for this carbonylation process (Scheme 47) involves the initial
d

formation of the manganese alkyl complex 49 upon reaction of the manganate anion [45]–
with alkyl iodide taking place either via SN2 nucleophilic substitution, or by SET followed by
te

recombination of tightly caged (CO)5Mn• and R• radicals. The preferred occurrence of the
latter mechanistic pathway was demonstrated by an ESR study revealing the presence of these
p

radical species, and by the observation of an inhibiting effect of the radical scavenger
ce

galvinoxyl. The alkyl complex 49 further undergoes a carbonylation to produce the acyl
complex 50, ultimately reacting with methanol to release the final ester with concomitant
Ac

generation of the manganese hydride 44. Finally, a simple deprotonation of 44 regenerates the
starting manganate [45]–, thereby closing the cycle.

53
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Edited June 30

Mn 2(CO) 10

HCO3 +2e R I

(CO) 5Mn
2
CO3 [45] I

t
ip
(CO) 5 MnH (CO) 5MnR
44 49

cr
OMe CO

us
R
(CO) 5MnCOR
O
50
MeOH

an
Scheme 47. Proposed mechanism for the Mn-catalyzed carbonylation of alkyl iodides [76]
M
It is worth noting, that the carbonylation of CyI can be also efficiently catalyzed by 4%
of neutral Mn2(CO)10 or (CO)5MnSnPh3 precursors under UV irradiation in the presence
methanol to give the corresponding CyCO2Me ester in 88%, and 92% yield, respectively [76,
d

77].
te

At higher CO pressure ester or amide products are obtained in excellent yields (Scheme
48) [78]. Contrary to the low CO pressure procedure [76, 77], the present one is equally
p

efficient for primary, secondary, and tertiary alkyliodides. Importantly, unlike what is
ce

observed with Pd-based systems, no dicarbonylation side-products are obtained.

O
Nu Nu
2.5% Mn2(CO) 10, 45-75 atm CO, 5 eq NuH
Ac

R I R + R
hv (Xe lamp, Pyrex), C6H6, RT, 4-16 h
O O
0%
Other examples:
O O
R Oct 2-Oct Ad Oct 2-Oct Ad
Ph
NEt2 NEt2 Nu BuO BuO BuO Et2N Et 2N Et 2N

75% 91% 54% 91% 80% 91% 86% 86%

O

NEt2
48%

54
Page 54 of 152
Edited June 30

Scheme 48. Mn-catalyzed carbonylation of alkyliodides in the presence of nucleophiles [78]

The proposed catalytic cycle starts with the generation of (CO)5Mn• (45•) by
photochemical cleavage of the Mn–Mn bond in Mn2(CO)10, and iodine atom abstraction from
RI to form (CO)5MnI and R• (Scheme 49). The formation of the alkyl radical intermediates
was confirmed by the formation of an acyclic carbonylation product from cyclopropyl iodide.

t
ip
The alkyl radical species is then carbonylated to form the corresponding acyl radicals, which
can be either trapped with 45• to give the acyl complex 50, or can abstract an iodine atom

cr
from (CO)5MnI to form the acyl iodide. The acyl intermediate 50 can be alternatively formed
by a recombination of R• and (CO)5Mn• radicals followed by a carbonylation of the resulting

us
alkyl manganese complex (CO)5MnR (path not shown in Scheme 49). Finally, the reaction
products are formed upon nucleophilic attack of the alcohol (amine) molecule onto the
corresponding acyl iodide, or onto the acyl manganese complex 50. In the latter case, the

an
regeneration of catalytically active species 45• from 44 can be performed either by
photochemical homolytic Mn–H bond cleavage, or by deprotonation (Nu = Et2NH) to give an
M
anionic manganate [45]–, which could contribute partially to the carbonylation process
according to Scheme 47.
Mn 2(CO) 10
d

hv
te

H . (CO) 5 Mn . R I

[45]
.
p

hv
ce

I
(CO) 5 MnH R (CO) 5MnI R .
Nu 44 O
Ac

R
CO
O

NuH
(CO) 5 MnCOR RCO .
50

(CO) 5 Mn
.

Scheme 49. Proposed mechanism for the Mn-catalyzed photochemical carbonylation of

alkyliodides in the presence of nucleophiles [78]

55
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Edited June 30

4. Mn-catalyzed transformations of alkenes

4.1. Alkene hydrogenation and hydroformylation
Mn2(CO)10 catalyzes the hydrogenation of simple alkenes at elevated temperature and
high H2 pressure [79]. Under optimized conditions (S/C ratio of 75, dioxane, 160 °C, 200 atm
of H2) ca. 95% conversion was achieved for 1-octene after one hour affording ca. 90% of

t
ip
octane and a mixture of internal octenes (5%), whereas Mn2(CO)10 was recovered in 75%
yield. The hydrogenation of 2-octene yields a similar product distribution (89% octane and

cr
3% of isomeric alkenes) but proceeds slower (92% conversion after 3 h under the same
reaction conditions).

us
The hydrogenation of several aromatic compounds with syngas could be also catalyzed
by Mn2(CO)8(PBu3)2 under harsh conditions (S/C ratio of 20, 70 atm of 1:1 CO/H2, 200 °C, 2-
5 h) [80]. The reaction is efficient for the hydrogenation of acridine only, affording a

an
quantitative GC yield of 9,10-dihydroacridine, whereas for antracene and quinoline only 30%,
and 33% GC yields of 9,10-dehydroantracene, and 1,2,3,4-tetrahydroquinoline were observed,
respectively. A Mn2(CO)10-catalyzed reduction of nitrobenzene with water shift gas could be
M
also realized in 20% yield (TON ca. 200) under similar reaction conditions (S/C ratio of 1000,
25% aqueous NMe3, THF, 180 °C, 2 h) [81].
d

Mn-catalyzed hydrogenation of 1-octene can take place at milder conditions (S/C ratio
of 135, 1 atm H2, without solvent, RT) under UV light activation [82]. The use cis-
te

(CO)4(PPh3)MnH as precatalyst led to octane (TOF 10 h–1) along with a mixture of 2-octenes
(TOF 30 h–1) as a result of the isomerization of the starting substrate. In the absence of
p

hydrogen, alkene isomerization only was observed (TOF 22 h–1). The σ-alkyl complex cis-
ce

(CO)4(PPh3)MnMe can also be used as precatalyst, albeit with a reduced efficiency (TOF for
1-octene hydrogenation of 7 h–1).
The hydroformylation of cyclohexene catalyzed by Mn2(CO)10 (S/C ratio of 41, 200 atm
Ac

1:1 CO/H2, hexane, 5.5 h) proceeds very sluggishly even at 175 °C to give a 9/90/1
CyCHO/cyclohexene/CyCH2OH mixture, the latter product resulting from reduction of the
aldehyde [79]. Though up to 96% cyclohexene conversion could be obtained at higher
temperature (235 °C), the reaction clearly lacks selectivity due to competitive alkene
hydrogenation (47%), formation of CyCH2OH (40%), and HCO2CH2Cy (8%) as major
products with only trace amount of CyCHO (1%).
The Mn2Rh2 cluster 51 (Figure 2) was used as pre-catalyst for the hydroformylation of
styrene, leading to the quantitative formation of the corresponding aldehydes under mild
conditions (S/C ratio of 200, 10-20 atm 1:1 CO/H2, 40-60 °C, heptane, 4-5 h) [83]. A

56
Page 56 of 152
Edited June 30

lowering of both the temperature and syngas pressure led to improve the linear/branched ratio
from 1:14.5 to 1:18.5. The authors tentatively proposed the formation of a catalytically active
bimetallic Mn/Rh species under the reaction conditions, though no experimental evidence was
provided.
O O
C C

t
Mn Rh Mn

ip
C Ph CO
O Rh
Ph
CO

cr
CO 51

Figure 2. A representation of the cluster 51

us
An impressive Rh/Mn synergism in catalytic alkene hydroformylation was reported by
Garland and coll. [84-86]. Indeed, though (CO)5MnH alone is inactive, its addition to catalytic

an
amounts of the rhodium precursor Rh4(CO)12 led to a very significant acceleration of
hydroformylation rate up to 300-500% for various alkene substrates (Table 6), including 3,3-
dimethylbutene-1 [84], cyclopentene [85], styrene and methylenecyclohexane [86]. Using in
M
situ IR monitoring, the authors were able to collect a full set of kinetics data for different runs
(Table 6), showing that the observed Mn/Rh synergism is the result of very efficient catalytic
binuclear elimination between the rhodium acyl complex (CO)3RhCOR and (CO)5MnH to
d

form the final aldehyde and a bimetallic complex, namely MnRh(CO)8, that rapidly activates
te

dihydrogen to regenerate the (CO)3RhH and (CO)5MnH hydride species (Scheme 50).
Though MnRh(CO)8 was not identified in the reaction mixture, parallel experiments based on
p

Rh4(CO)12 and (CO)5ReH allowed the detection of ReRh(CO)9, which is actually prone to
ce

activate molecular hydrogen (k = 38 min–1 under 4 MPa of CO) [87]. Taking into account a
molar (CO)5MnH/H2 ratio of ca. 0.005 for most of the catalytic experiments, kinetic data
clearly show that the manganese hydride complex is hundred times more efficient than
Ac

dihydrogen for the hydrogenolysis of the rhodium acyl intermediate (CO)3RhCOR (Scheme
50). Yet the role of the manganese hydride is not only to facilitate the final step of the
hydroformylation process. Indeed, the transformation of the starting rhodium precursor
Rh4(CO)12 into the catalytically active species (CO)3RhH is also significantly faster in the
presence of manganese hydride. For example, a t1/2 of 10 minutes is observed for Rh4(CO)12
in the hydroformylation 3,3-dimethylbutene-1 catalyzed by the mixed Rh/Mn system, as
opposed to 2 h required for a purely Rh-based system [84], a difference which can be
rationalized in terms of the well-known hydride-induced cluster degradation. The latter
process is also likely to be responsible for the observed reduced rate of catalyst deactivation

57
Page 57 of 152
Edited June 30

within the Rh/Mn system, as accumulation of the stable Rh6(CO)16 was not observed, even at
high degree of substrate conversion [84].

Table 6. Rh/Mn-cocatalyzed alkene hydroformylation in hexane (A – 3,3-dimethylbutene-1,

B – cyclopentene, C – methylenecyclohexane, D – styrene) [84-86]

t
Rh4(CO)12 Rh4(CO)12/(CO)5MnH CO H2 Temp, kRh kRh/Mn

ip
Alkene
mol % initial molar ratio (MPa) (MPa) °C (min–1) (min–1)

0.17 2.5 2.0 1.0 25 0.45 44.5

cr
A

B 0.12 2.0 2.0 2.0 17 0.31 37

us
C 0.14 2.85 2.0 2.0 17 0.04 26

D 0.055 5.0 5.0 0.5 35 3.4 192

an
M
d
p te
ce
Ac

58
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Edited June 30

H
CO
OC Rh
CO
CO

+ CO CO

t
H

ip
RCHO OC Rh CO

CO +

cr
R O
OC CO CO
Rh OC Rh

us
H H H
CO CO
MnRh(CO) 8H 2

an
+ H2 H2 (CO) 5MnH RCHO + H2

R O MnRh(CO) 8
R
M
OC Rh CO OC Rh CO

CO CO CO
R
d
+ CO
CO
+ CO CO
OC Rh
te

CO
R O CO
CO
p

OC Rh
CO
ce

CO

Scheme 50. Proposed catalytic cycle for the Rh/Mn-cocatalyzed alkene hydroformylation
[84-86]
Ac

4.2. Mn-catalyzed reactions of alkenes with silanes

A hydrosilylation of 1-pentene with heptamethylcyclotetrasiloxane catalyzed by
(CO)5MnSiPh3 was originally reported by Faltynek and coll. (Scheme 51) [88]. The reaction
proceeds efficiently under UV irradiation at RT giving the corresponding pentylsilane in
quantitative yield. By contrast, the latter compound is produced in lower yield (55%) under
thermal activation (180 °C), and is accompanied by alkenylsilanes (25%), and silane
dimerization products (20%). The low selectivity observed at high temperature was attributed

59
Page 59 of 152
Edited June 30

to the implication of free radical species, as further demonstrated by the observation of a

decrease of the reaction rate upon addition of the t-Bu2NO• radical.

Me 2 Me2 Me 2
Si Si Si
O O H O O Pent O O Pr
0.1% (CO) 5 MnSiPh 3
+ Me 2 Si Si

t
Me 2Si Si Me2 Si Si
no solvent

ip
O O Me O O Me O O Me
Si Si Si
Me2 Me 2 Me2

cr
+ UV, RT 100% 0%

180 °C 55% 25%

us
Scheme 51. Mn-catalyzed hydrosilylation of 1-pentene [88]

an
Mn2(CO)10 catalyze the hydrosilylation of 1-hexene with Et3SiH or (EtO)3SiH (0.5 eq.)
under mild conditions (2-4% Mn2(CO)10, toluene or THF, 40 °C) [89], but the reaction was
M
limited to 20-30% silane conversion due to a rapid catalyst deactivation.
An efficient Mn-catalyzed conjugated reduction of α,-unsaturated enones with PhSiH3
takes place under mild conditions [90]. The reaction is remarkably chemioselective regarding
d

the C=C bond reduction. Besides, it is quite sensitive to steric factors, allowing in particular
te

the selective reduction of the double bond with only one substituent only at the -position in
the presence of a ,-disubstituted enone moiety (Scheme 52). For less active silanes such as
p

Ph2SiH2 and PHMS the reaction is much slower and does not proceed at all for tertiary silane
such as Et3SiH.
ce
Ac

60
Page 60 of 152
Edited June 30

O O

H 3% Mn(dpm) 3 , 1.3 eq PhSiH 3 H

i-PrOH/DCE, RT
H H H H
O O
Other examples:
99%

t
ip
O O
O
O
Ph
Pent

cr
O

99% 25% 50% 74%

us
OTBS

an
O O

O O
OCPh3 OCPh 3
M
50% 100% a 100% a

Scheme 52. Mn-catalyzed reduction of conjugated enones with PhSiH3 (a i-PrOH/DCM was
d

used instead of i-PrOH/DCE) [90]

te

The reaction mechanism (Scheme 53) is likely to include the initial formation of a
p

Mn(III) hydride active species 52 from Mn(dpm)3, silane and isopropanol. The intermediate
ce

52 further undergoes an irreversible nucleophilic addition to the enone substrate to form the
Mn(III) enolate 53, affording upon solvolysis the final saturated ketone along with the Mn(III)
alkoxide 54. The starting hydride 52 is then regenerated upon reaction with another silane
Ac

molecule. The irreversible character of the key hydride nucleophilic attack step of this
catalytic cycle, 5253, was confirmed upon using deuterated silane PhSiD3 in i-PrOH,
thereby leading to a selective incorporation of only one deuterium label at the -position.
Interestingly, when the same catalytic mixture was used under an oxygen atmosphere, a
selective α-hydroxylation of the enones was observed instead (Scheme 54) [91]. The reaction
results initially in the formation of a mixture of the corresponding α-hydroperoxy- and α-
hydroxyketones, which can be readily transformed into the -hydroxylated products upon
subsequent treatment with triethylphosphite.

61
Page 61 of 152
Edited June 30

(III)
Mn(dpm) 3 + PhSiH 3 + i-PrOH

dpmH + PhSiH2OPr-i
(III)
PhSiH2 OPr-i HMn(dpm) 2
52 O

t
ip
PhSiH 3

cr
(III) (III)
i-PrOMn(dpm) 2 H OMn(dpm) 2
54 53

us
H

an i-PrOH
M
H O
Scheme 53. Proposed catalytic cycle for the Mn-catalyzed reduction of conjugated enones [90,
91]
d
p te
ce
Ac

62
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Edited June 30

O O
OH
H 3% Mn(dpm) 3 , 1.3 eq PhSiH 3 , O2 H

i-PrOH/DCE, 0 °C or RT, then 1.1 eq P(OEt) 3

H H H H
O O
Other examples:
85%

t
HO Me

ip
HO Me OH OH O
O
O O O
Pent

cr
O Ph OH

59% 87% 51% 50% 73%

us
OTBS
HO Me
O O

an
HO O O

HO O HO O
OCPh 3 OCPh3
M
70% 78% >95% >95%

Scheme 54. Mn-catalyzed α-hydroxylation of conjugated enones [91]

d
te

The reaction typically proceeds in good to excellent yields, and with a remarkable regio-
and stereoselectivity. It is worth noting that even ,-disubstituted enones such as mesityl
p

oxide can be efficiently hydroxylated in the presence of oxygen. This can be reasonably
attributed to stronger nucleophilic properties of the Mn(V) peroxohydride complex 55,
ce

formed from the corresponding Mn(III) hydride precursor 52 in the presence of oxygen
(Scheme 55), than the hydride complex 52 itself. It is then proposed that the Mn(V) enolate
Ac

56 rapidly evolves through an homolytic cleavage of the Mn–O bond to give free or caged -
ketoalkyl radicals, which undergoes a classic radical transformation into the corresponding
hydroperoxide compounds, partially reduced into the alcohol products under the reaction
conditions. The implication of free radical species in this process was indicated by a different
alkoxylation regioselectivity observed for the substrates giving more stable radicals than the
-ketoalkyl ones (see Scheme 55 and similar examples below). The enolate 56 can be
hydrolyzed to give saturated ketones as side products if traces of acid are present in the
reaction mixture. The resulting Mn(IV) complex 57 can regenerate the catalytically active
hydride intermediate 55 upon hydrogen atom abstraction from the silane, or from the solvent.

63
Page 63 of 152
Edited June 30

(III) (III)
Mn(dpm) 3 + PhSiH 3 + i-PrOH HMn(dpm) 2 + dpmH + PhSiH2 OPr-i
52

O2

. (V) O

t
PhSiH 2 or i-PrO . H(dpm) 2Mn

ip
55 O
O

cr
PhSiH 3 or i-PrOH

us
(IV) O (V)
(dpm) 2Mn OMnO 2(dpm) 2
O 56
57

OH OOH an
M
[H] O2
.
H.
O O O
d

Scheme 55. Proposed catalytic cycle for Mn-catalyzed enones α-hydroxylation [91]
te

The good level of stereoselectivity typically observed in the Mn-catalyzed enone α-

p

hydroxylation process could be exploited for the synthesis of optically active products using
ce

substrates bearing pyrrolidine chiral auxiliary (Scheme 56) [92]. The reaction led to the
corresponding α-hydroxyketones in good yield and synthetically useful de level for the
substrates with minimal steric crowding only.
Ac

The mild operational conditions of this Mn-catalyzed α-hydroxylation protocol make

this method compatible with elaborated organic molecules, such as Avermectin B1, an
industrially produced crop protection agent [93].

64
Page 64 of 152
Edited June 30

2-Naph 2-Naph
OH
5% Mn(dpm) 3, O2 , 2 eq PhSiH 3
R N i-PrOH, 0 °C, 7-15 h R N

O O
2-Naph 2-Naph

2-Naph R Pr Hept n-C 11H 23 n-C 15H 33 i-Pr

t
OH 77% 87% 81% 81% 62%

ip
Other example: Et N de 80% 82% 92% 94% 56%

O 2-Naph

cr
84% (72% de )

us
Scheme 56. Mn-catalyzed α-hydroxylation of conjugated enones bearing pyrrolidine chiral
auxiliary [92]

an
Other types of alkenes bearing electron-withdrawing groups, namely esters, amide,
nitrile and nitro, also undergo Mn-catalyzed hydroxylation under similar reaction conditions
M
[94, 95]. While this method is very efficient in the case of ,-unsaturated esters (Scheme 57)
[94], it is less successful for the other types of substrates, leading to lower chemoselectivity
and moderate products yields (Scheme 58) [95]. Noteworthy, the amount of -hydroxylation
d

isomer increases progressively when substituents capable of stabilizing a radical center are
te

installed in the -position relative to ester group, actually confirming the occurrence of a
radical reaction pathway (Scheme 55).
p
ce
Ac

65
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Edited June 30

OH
R OBn 2% Mn(dpm) 3 , 2 eq PhSiH 3, O2 R OBn
i-PrOH, 0 °C, 1.5-6 h, then Na2 S2 O3 aq
O O

R H Me Pr Pent Hept CO2Me

91% 91% 86% 94% 84% 76%

Other examples:

t
ip
OH OH O O Ph OEt
OBn OBn
Ph

cr
EtO OEt
OH O
O O OH
92% 94% 82% 73%

us
Ph OEt OH OBn OH
Ph OEt + OBn
O
+ OH O
OH

an
O O
65% 11% M 12% 24%

Scheme 57. Mn-catalyzed α-hydroxylation of ,-unsaturated esters [94]

OH
d

R 3% Mn(dpm) 3, 1.3 eq PhSiH 3 , O 2 R Bu CH2Bu-t Cy

CN i-PrOH, 0 °C  RT, 1-20 h R
CN 44% 27% 54%
te

Other examples:

HO CN
p

HO OH OH
CN OH
ce

CN CN
+ + CN

53% 10% 13% 27% 29%

Ac

OH CN OH CN
Ph + Ph Ph
CN + Ph Ph
CN CN CO2 Me NO2
CN CO2Me
10% 56% 18% 42% 20%

OH CO2Me CN CN
Ph
CO2Me
+ Ph HO N + Ph N
CO2 Me
CO2Me Ph
O O
71%
42% 44% 24%

66
Page 66 of 152
Edited June 30

Scheme 58. Mn-catalyzed α-hydroxylation of other types of activated alkenes [95]

The same Mn(dpm)3/PhSiH3/i-PrOH combination can be used for the

hydrohydrazination of unactivated alkenes by di(tert-butyl)azodicarboxylate (Scheme 59) [96,
97]. This protocol provides an easy access to various Boc-disubstituted hydrazines, which
could be easily deprotected using 8M solution of HCl in THF, and further transformed into

t
ip
the corresponding amine derivatives by reduction with Zn/AcOH. Such a procedure is of
special importance for the preparation of volatile commercially unavailable cyclopropyl and

cr
cyclobutylamine derivatives.

us
Boc NHBoc
N Boc

2% Mn(dpm) 3 , 1.5 eq BocN=NBoc N

Ph Ph + Ph

an
NHBoc
1 eq PhSiH 3 , i-PrOH, 0 °C, 2 h
80% 14%

Other examples (R = NBocNHBoc):

M
R R R R R R R
Et
Et
Ph
d
O
78% 51% 66% 77% 88% 94% 81%
te

R R R
R R
R
p

H2 N
ce

90% 79% 95% 98% 74% 60-80%

O
R R R O O R
Ac

OH CO2 Et CN O N N
R
72% 88% 45% 75% (de 62%) 83%

Scheme 59. Mn-catalyzed alkene hydrohydrazination with BocN=NBoc [96, 97]

The manganese-based catalytic is much more active than a closely related cobalt-based
one, especially for sterically crowded alkene substrates, as illustrated by the respective TON
values obtained for the hydrohydrazination of 4-phenylbutene-1 – 44 for Co and 430 for Mn –

67
Page 67 of 152
Edited June 30

and tetramethylethylene – 3 for Co and 240 for Mn – using reduced 0.1% of Co- or Mn-based
catalysts. The use of the Mn-based catalyst was also beneficial (20-50% increase of yields) for
substrates bearing potentially coordinating functional groups such as alcohols, amines, and
nitrogen heterocycles. Owing to the remarkable activity of the Mn-based catalyst, it is even
possible to use less reactive silanes such as Ph2SiH2 and PHMS, though this requires
prolonged reaction times (15 h) at RT. However, slight disadvantages inherent to the very

t
ip
high reactivity of the manganese active species are a lower Markovnikov selectivity in the
case of simple terminal alkene such as 4-phenylbutene-1 (5.5:1 isomers ratio), and to the

cr
impossibility to catalyze alkene hydroazidation reaction due to a rapid catalyst desactivation.
The hydrohydrazination of α,-unsaturated esters and amides bearing a chiral auxiliary

us
was also reported [97, 98]. While the reaction was only moderately efficient in the case of the
crotyl ester bearing a D-pantolactone-based moiety (Scheme 60) [97], the implementation of a

an
slightly modified protocol to several amides with Oppolzer camphorsultam auxiliary provided
the corresponding products in good yield with a synthetically useful level of
diastereoselectivity (Scheme 60) [98].
M
d

BocHN Boc
5% Mn(dpm) 3 , 2 eq BocN=NBoc N
te

R N 2 eq PhSiH 3 , i-PrOH, 0 °C, 1-1.5 h R N

S S
O O
O O O O
p

R H Me Pr Hept i-Pr Ph(CH 2) 2 MeS(CH 2 ) 2

ce

56% 84% 81% 80% 78% 68% 72%

de 82% 96% 92% 92% 98% 94% 92%
Ac

Scheme 60. Mn-catalyzed hydrohydrazination of α,-unsaturated amides with camphorsultam

chiral auxiliary [98]

The proposed catalytic cycle (Scheme 61) includes an insertion of the alkene into the
Mn–H bond of the Mn(III) hydride intermediate 52 to form the σ-alkyl complex 58. The latter
reacts with azodicarboxylate to give the Mn(III) amide complex 59 via a sequence of Mn–C
homolytic cleavage, trapping of the resulting radical with BocN=NBoc, and final
recombination of the resulting N-centered radical with Mn(dpm)2. The occurrence of free or
caged alkyl radical species in the catalytic cycle was confirmed by the preferred formation of
68
Page 68 of 152
Edited June 30

radical rearrangement products for vinylcyclopropane and 1,6-diene substrates (Scheme 62)
[97]. Finally, the solvolysis of 59 leads to the formation of the final hydrohydrazination
product and regenerates the initial hydride 52.
(III)
Mn(dpm) 3 + PhSiH 3 + i-PrOH

t
dpmH + PhSiH 2OPr-i

ip
PhSiH 2 OPr-i
(III)
PhSiH 3 R
HMn(dpm) 2

cr
52

us
Boc (III) R
(III)
i-PrOMn(dpm) 2
R N H Mn(dpm) 2
54
N H 58

an
Boc
H M
i-PrOH
Boc
(III)
R N Mn(dpm) 2 (II)
R
Mn(dpm) 2 H
d
N 59

.
Boc
te

H Boc
R N .
Boc
p

N
N N
Boc
Boc
ce

Scheme 61. Proposed catalytic cycle for the Mn-catalyzed alkene hydrohydrazination [97]
Ac

2% Mn(dpm) 3, 1.5 eq BocN=NBoc X X O C(CO2 Et)2

X 88% 93%
1 eq PhSiH3 , i-PrOH, 0 °C, 2 h
dr 2.5:1 9:1
N(Boc)NHBoc

Scheme 62. Mn-catalyzed hydrohydrazination of 1,6-dienes with concomitant 5-exo-trig

radical cyclization [97]

4.3. Other Mn-catalyzed alkene transformations

69
Page 69 of 152
Edited June 30

MnCl2-catalyzed efficiently the 1,2-silylmagnesiation of conjugated dienes (Scheme 63)

[99]. Interestingly, in the case of isoprene the less substituted double bond reacts selectively
to give a dialkylmagnesium species 60.

R R
R 1.6 eq PhMe2 SiMgMe, 8% MnCl 2 +
E

t
SiMe2 Ph SiMe2 Ph
-80°C

ip
THF, 0 °C, 10 min
MgMe E

60
R H H Me Me Me Me

cr
E D Me H D Me All
48% 63% 70% 74% 83% 83%

us
Other examples:

SiMe 2Ph SiMe2 Ph SiMe 2Ph

an
SiMe 2Ph

R OH OH OH
53% 47%
R Bu Ph R H Me
M
88% 95% 80% 90%

Scheme 63. Mn-catalyzed silylmagnesiation of conjugated dienes [99]

d
te

Noticeably, the quenching of the allylmagnesium intermediates 60 with the

electrophiles has to be performed at –80 °C for optimal product selectivity since at RT these
p

species undergo a partial isomerization into 60’ (Scheme 64). The latter process is
synthetically useful in the case of 1,4-butadiene allowing the selective preparation of both
ce

homoallyl and vinylsilane products.

Ac

1.6 eq PhMe 2 SiMgMe, 8% MnCl2 Me2 CO

SiMe 2Ph -80°C SiMe 2Ph
THF, 0 °C, 10 min
MgMe
OH
60
80%
RT
OH

MgMe Me2 CO
RT SiMe2 Ph
SiMe2 Ph
60' 90%

70
Page 70 of 152
Edited June 30

Scheme 64. Mn-catalyzed synthesis of homoallyl and vinylsilane derivatives by

silylmagnesiation of 1,4-butadiene [99]

The addition of AllMgCl to allenes catalyzed by MnCl2 proceeds in a highly

regioselective manner giving, after quenching of intermediates 61 with electrophiles such as
H2O, I2, AllBr, AcCl, or PhCHO, the corresponding 1,5-dienes in moderate to good yields

t
ip
(Scheme 65) [100]. The observed high regioselectivity was interpreted as the result of a
preferred coordination of the most substituted double-bond of the allene onto the manganate

cr
center, followed by a migration of allyl group onto the most substituted carbon atom, thereby
releasing the steric repulsion with the adjacent coplanar hydrogen atom. In the case of 1,2-

us
cyclononadiene the reaction proceeds with an excellent stereoselectivity, whereas for other
substrates a mixture of isomers were always obtained.

.
Dec
3 eq AllMgCl, 20% MnCl 2
2 eq HMPA, THF, RT, 15 h
ClMg an All
Dec
E+

E
All
Dec
M
61
E H I All Ac
Other examples: 78% 68% 69% 57%
E
d

E
All
All Pent All
te

E Pent
p

E H I Ac E H I Ac E H I All Ac Ph(H)COH
76% 62% 50% 58% 40% 34% 70% 63% 71% 45% 47%
ce

E/Z 1:99 99:1 99:1

Scheme 65. Mn-catalyzed allylmagnesiation of allenes [100]

Ac

Interestingly, in the presence of oxygen, selective diallylation of allenes is achieved in

good yield and, again, with excellent stereoselectivity for 1,2-cyclononadiene (Scheme 66)
[100]. Though the exact role of oxygen is not totally clear, it was suggested that it could
indirectly promote a reductive elimination from the vinyldiallylmanganate intermediate, as
well as a hetero-coupling of the vinyl Grignard intermediate 61 with the excess of AllMgCl.

71
Page 71 of 152
Edited June 30

Other example:
All
. All
All
5 eq AllMgCl, 20% MnCl2
THF, RT, 9 h then O 2, 40 h Pent All
Pent
64%
77% 2:3 mixture of isomers

t
ip
Scheme 66. Mn-catalyzed diallylation of allenes in the presence of oxygen [100]

cr
Radical cyclizations of iodoamides bearing a pendant alkene moiety can be promoted
more efficiently by Mn2(CO)10 under irradiation, rather than by toxic tin hydrides, to give the

us
expected heterocyclic products in 78% yield (Scheme 67) [101, 102]. Importantly, in the
presence of a hydrogen donor (2 eq of i-PrOH), or in the presence of a spin trapping reagent

an
(TEMPO), it was possible to obtain the corresponding radical coupling products in 54%, and
78%, respectively.
M
I TEMPO
I

10% Mn 2(CO) 10
O or O or O
O N N N N
d
UV, CH2 Cl2, RT, 1-5 h
p-An p-An p-An p-An
te

78% 54% 78%

no additive 2 eq of i-PrOH 1.1 eq of TEMPO

p

Other examples:
ce

Cl Cl TEMPO Br TEMPO
Cl Cl Br
Ac

O O O N O
N N N

p-An p-An p-An p-An

43% (dr 1:1) 53% 65% 72%

Scheme 67. Mn2(CO)10-promoted radical cyclization of iodoamide derivatives [101, 102]

The exo-5-trig cyclization of various 1,6-dienes can be also efficiently induced by

manganese radicals in the presence of BrCCl3 (Scheme 68) [102, 103].

72
Page 72 of 152
Edited June 30

(A ) 10% Mn 2 (CO) 10, BrCCl3, UV, RT, 2 h, CH2Cl2 X

X
or (B ) 20% (CO) 5 MnBr, BrCCl3, CH2 Cl2 /NaOH aq
Br CCl3
X C(CO 2Et)2 C(O)CCl3 NTos O
A 89% 60% 60% 87%
dr 8:1 6.6:1 6.6:1 6:1
B 99% - - 99%

t
ip
dr 10:1 - - 6:1

cr
Scheme 68. Mn2(CO)10-promoted exo-5-trig cyclization of 1,6-dienes in the presence of
BrCCl3 [102, 103]

us
Here, the manganese radical (CO)5Mn• abstracts a bromine atom from BrCCl3 to give
the Cl3C• radical species that undergoes addition to the alkene double bond, followed by a

an
cyclization, and again bromine atom abstraction from BrCCl3. The reaction efficiency can be
further improved using (CO)5MnBr as a pre-catalyst in biphasic CH2Cl2/NaOHaq mixture in
M
the presence of a phase transfer catalyst [103].
Manganese pentacarbonyl bromide (CO)5MnBr catalyzes the cyclopropanation of
styrene with an ene-yne ketone (Scheme 69) [104], albeit in less efficient manner than group
d

6 metals complexes (CO)5M(THF) (M = Cr, Mo, W). This could be rationalized in terms of a
te

slower CO for alkyne substitution reaction in the absence of thermal or photochemical

activation.
p
ce

Ph Ph

O 5% (CO) 5MnBr
+ Ph O
THF, RT, 24 h
Ac

20 eq

Ph

24% (cis/trans 9:91)

Scheme 69. (CO)5MnBr-catalyzed cyclopropanation of styrene [104]

A unique example of Mn-catalyzed ring-opening polymerization of norbornene (0.35%

of cat, 1.5% of EtAlCl2, CH2Cl2, 0 °C to RT, 1 h) involving the complex
(12[ane]P3Et3)Mn(CO)2Br - where 12[ane]P3Et3 stands for the macrocyclic 1,5,9-triethyl-
1,5,9-triphosphacyclododecane ligand - to produce atactic polynorbornene in ca. 60% yield

73
Page 73 of 152
Edited June 30

was reported [105]. Though its rhenium analogue (12[ane]P3Et3)Re(CO)2Cl exhibits a similar
activity (12.6 vs. 14.6 kg mol–1 for Mn and Re, respectively), the Mn-based catalytic system
provides much lower molecular weight polymers (Mw 3710 (PDI 2.9) for Mn vs. Mw 217500
(PDI 5.1) for Re).

t
5. Mn-catalyzed transformations of alkynes

ip
In 1997 Oshima and coll. reported a MnI2-catalyzed cis-addition of AllMgBr to
homopropargylic ethers to give, after quenching of the vinylmagnesium intermediate 62 with

cr
electrophiles such as H2O, AllBr, PhCHO, or HexCHO, the corresponding 1,4-dienes in 72-
92% yields (Scheme 70) [106, 107]. In addition to MnI2, the reaction can also be catalyzed by

us
Mn(acac)3, and even with the organometallic manganese precursors Cp’Mn(CO)3 or
Mn2(CO)10. Noticeably, the presence of an adjacent oxygen atom in the alkyne substrate is
mandatory since 6-docecyne is completely unreactive even under prolonged reflux. It is

an
assumed that the stabilization of a π-alkyne manganese complex by formation of a 5-
membered chelating cycle plays a key role in the reaction. In line with this hypothesis, a
M
significant decrease of product yield was observed for substrates leading to a less stable 6-
membered chelating intermediate.
Hex
d
Hex
RO 1.5 eq AllMgBr, 3% MnI2
RO All E+
RO All
Hex Et 2O, RT, 3 h
te

MgBr E
62
p

Other examples:
MeO R Me Me Me Me Bn THP
Ph
ce

Pr E H All PhCH(OH) HexCH(OH) H H

MeO All
Et 83% 77% 92% 87% 77% 74%
All
Ac

72% 74%

Pent
All
BnO
42%

Scheme 70. MnCl2-catalyzed addition of AllMgBr to homopropargylic ethers [106, 107]

Mn-catalyzed allylmagnesiation of propargylic ethers proceeds via the elimination of

the alkoxide group to give the allene products in moderate yields (Scheme 71). Interestingly,

74
Page 74 of 152
Edited June 30

in the case of the allyl-substituted ether, a tetrahydrofurane derivative was formed as a major
product.
All
All Hex
RO 1.5 eq AllMgBr, 3% MnI2 or Mn(acac) 3
. +
Hex Et 2O, RT, 3 h
Hex
O

t
ip
R = Me 56% 0%
R = Me 2C=CHCH2 56% 0%
R = All 15% 27%

cr
Scheme 71. MnCl2-catalyzed addition of AllMgBr to propargylic ethers [106, 107]

us
The manganese derivative 64 exhibiting a similar tetrahydrofuran scaffolds was
proposed as intermediate in the catalytic formal addition of allyl and vinyl groups to a CC
triple bond, actually occurring upon treatment of vinylhomopropargylic ethers with an excess

an
of AllMgBr in the presence of Mn(acac)3 (Scheme 72) [106, 107]. The proposed reaction
mechanism includes an allylmanganation of the alkyne moiety, followed by a rearrangement
M
of the resulting vinylmanganate intermediate 63 into the cyclic compound 64 that finally
undergoes ring opening and transmetallation to give 65, the latter releasing the final dienes
after hydrolysis.
d
te

Hex
O HO All
2.5 eq AllMgBr, 3% Mn(acac) 3
Hex
p

THF, RT, 9 h then 0.5M HCl

R
ce

R H Hex R
75% 65%
(II)
(All) 4Mn(MgBr) 2
AllMgBr
Ac

Hex (II) Hex

Hex All BrMg(All) 3 MnO All
O All (II)
Mn(All) 3MgBr
(II)
O R
R Mn(All) 3MgBr
63 R 64 65

Scheme 72. Mn-catalyzed addition of AllMgBr to vinylhomopropargylic ethers [106, 107]

75
Page 75 of 152
Edited June 30

As for the diallylation of allenes (Scheme 66), the addition of oxygen here too can
induce a selective diallylation of the alkyne (Scheme 73) [106, 107]. Cp’Mn(CO)3 is the most
efficient precatalyst, whereas Mn(acac)3 and MnI2 afford lower yields and selectivity.

Hex
RO 4 eq AllMgBr, 10% Cp'Mn(CO) 3 RO All

t
Hex THF, RT, 2 h under Ar then 12 h under air

ip
All
MeO

cr
Pr R Me Bn THP
Other example:
Et 80% 78% 35%
All All

us
78%

an
Scheme 73. Mn-catalyzed alkyne diallylation with AllMgBr [106, 107]

Mn-catalyzed silylmagnesiation can be performed even for substrates unable to undergo

M
an allylation, namely terminal and internal aliphatic alkynes, without pendant ether moiety
(Scheme 74) [99]. However, the presence of an adjacent oxygen atom in the alkyne
substituent again leads to an increase of both reaction yield and regioselectivity.
d
te

R R' R R'
1.6 eq PhMe 2 SiMgMe, 8% MnCl2
R R' +
THF, 0 °C  RT, 1-2 h then H 2O
p

SiMe2 Ph PhMe 2Si

A B
ce

R BnOCH2CH 2 BnOCH2 CH2 THPCH2 CH2 Hex Dec Pent

R' H Hex H H H Pent
Ac

90% 95% 90% 40% 50% 95%

A:B >95:5 73:27 85:15 80:20 76:24 -

Scheme 74. MnCl2-catalyzed silylmagnesiation of terminal and internal alkynes [99]

The vinylmagnesium intermediates 66 can be trapped with other electrophiles such as

AllBr (68%, 4:1 isomers ratio) and ArCHO, unexpectedly giving in the latter case a mixture
of cyclic silyl ethers. The later may be seen as the result of an intramolecular nucleophilic
attack of the alkoxide anion onto the silicon atom with elimination of PhMgMe, partially

76
Page 76 of 152
Edited June 30

reacting with aldehydes to form the corresponding secondary alcohols Ar(Ph)C(H)OH indeed
detected in the reaction mixture (Scheme 75).

BnO BnO
Hex Hex Hex
1.6 eq PhMe 2 SiMgMe
BnO +
8% MnCl 2, THF, RT, 2 h

t
MeMg SiMe2 Ph PhMe 2 Si MgMe

ip
66 66'
ArCHO

cr
BnO BnO BnO BnO
Hex Hex Hex Hex

us
+ PhMgMe +
SiMe 2 Me2 Si Ar SiMe2 Ph PhMe 2 Si Ar
Ar Ar
O O OMgMe MeMgO

an
A B

Ar = Ph 65% (A:B 5:1)

Ar = p-An 70% (A:B 7:3)
M
Scheme 75. Reactions of vinylmagnesium compounds 66 with aromatic aldehydes [99]
d

Finally, even the less reactive PhMgBr can be used for the Mn-catalyzed addition to
internal aliphatic and aromatic alkynes upon heating at 100 °C in toluene (Scheme 76) [108].
te

Yet, as in the case of allylations (see above), the reaction fails for aliphatic alkynes lacking an
adjacent functional group, whereas aryl-substituted acetylenes are generally more reactive.
p

Alcohols, ethers and aliphatic amines were suitable activators for aliphatic alkynes, whereas
ce

thioether and N(Me)Ph substituents failed to promote the addition reaction. It is worth noting
that the addition of PhMgBr proceeds with a remarkable regioselectivity, given that the
Ac

carbon atom bearing aryl- or alkyl substituents possessing donor functional groups
coordinates preferentially to the Mn center. The chelate effect can be clearly illustrated by
addition of PhMgBr to different anisyl-substituted acetylenes (Scheme 76). Noticeably, its
addition to propargylic alcohol HexCCCH2OH leads in fine to the allene derivative
Hex(Ph)=C=CH2 in 70% yield. The vinylmagnesium intermediates can be even trapped with
other electrophiles such as AllBr or PhCHO to give the corresponding tetra-substituted alkene
products in good yields.

77
Page 77 of 152
Edited June 30

Hex R
3 eq PhMgBr, 10% MnCl2 R Ph p-Tol o-An m-An p-An
Hex R
toluene, 100 °C, 7 h then E + 66% 63% 80% 63% 38%
Ph H

Other examples:
F
R
Hex

t
Hex Hex Hex

ip
Ph H NMe2 F
Ph H Ph H Ph H
R OH OMe OBn NEt2
94% 47% 71%

cr
50% 71% 74% 59%

us
Hex Ph Ph Hex Hex
. NMe2 NMe2
Ph Ph H Ph All Ph OH
70% a Ph

an
60% 67% 65%

Scheme 76. MnCl2-catalyzed addition of PhMgBr to internal alkynes (a from 2-nonyl-1-ol)

M
[108]

Tsuji and Nakamura [109], and Kuninobu and Takai [110, 111], reported almost
d

simultaneously a highly regioselective preparation of tetrasubstituted benzenes by [2+2+2]

cycloaddition using (CO)5MnBr as a precatalyst (Scheme 77). Noticeably, only trace amounts
te

of classic alkyne trimerization products are observed. A variety of enolizable 1,3-diketones

and -ketoesters and terminal alkynes can be successfully engaged, whereas cyclic 1,3-
p

diketones and internal alkynes are inert. The reaction is tolerant to several important
ce

functional groups such as alkene, Br, BPin, or CF3, but quite sensitive to steric factors as the
coupling fails for -ketoesters bearing bulky Cy or t-Bu groups, as well as for more sterically
Ac

demanding alkyne such as o-TolCCH.

78
Page 78 of 152
Edited June 30

Ph O
(A) 10% (CO) 5MnBr, 10% NMO,
R
O O MgSO 4, toluene, 65 °C, 3-48 h OEt
+ R H
Ph OEt (B) 5% (CO) 5 MnBr, MS 4Å,
2.5-3 eq R
neat conditions, 80 °C, 24 h

R Ph o-An p-An 2-Naph p-BrC 6H 4

t
A 94% - 77% 65% 84%

ip
B 88% 74% 77% - 86%
O Other examples:

cr
Ph
R O
Ph OEt
Ph MeO

us
R Me OMe OEt OBn OAll
OMe
A 98% - 87% 84% 81%
71% (A)
B 69% 65% 85% - -

an
Ph
O
p-An O O Ph OEt
Ph Ph
M
OEt OEt R R

Ph Ph
75% (A ) 83% (A) R p-CF3 C6 H 4 p-PinBC 6 H4
d
A 83% 65%
te

Ph O Ph O O O
R R
OEt + OEt OEt + OEt
p

R R R R R R
ce

R = Hex 69% ( A ) 25% ( A ) R = CH2CH 2Ph 64% (B ) 24% (B )

R = Bn 61% (A) 21% (A)
Ac

Scheme 77. Mn-catalyzed [2+2+2] cycloaddition of terminal alkynes with 1,3-dicarbonyl

compounds [109-111]

Typically, for -ketoesters, the cycloaddition proceeds equally well under reaction
conditions A or B (see Scheme 77) with both aliphatic and aromatic alkynes, although the
regioselectivity of the cycloaddition is largely better in the latter case. For acetylacetone,
protocol A and B afford the tetra-substituted arene product in 98% [109], and 69% yield [110,
111], respectively, the latter procedure leading to two by-products (Scheme 78) [110, 111].

79
Page 79 of 152
Edited June 30

The reaction can be driven selectively to the formation of 2-methyl-1,4-diphenylbenzene upon

addition of water and a Lewis acid (Scheme 78).

O O O OH O
Ph Ph
5% (CO) 5MnBr, 5% Sc(OTf)3
+ + +

t
toluene/H 2O 1:1, 80 °C, 24 h
Ph H Ph Ph Ph

ip
2 eq 16% 68% 4%
69% (A ) 5% (A ) 7% ( A)

cr
Scheme 78. Mn-catalyzed reaction of acetylacetone with phenylacetylene [110, 111]

us
The mechanism of this original [2+2+2] cycloaddition was studied in detail by
Nakamura and coll. for acetylacetone and different terminal alkynes RCCH (R = H, Me, Ph)

an
using DFT calculations (Scheme 79) [112]. The entry point of the catalytic cycle would be
complex 67 initially formed upon reaction of (CO)5MnBr, acetylacetone and the terminal
M
alkyne. Complex 67 bearing two η2-alkyne and an acac ligands could evolve into the
intermediate 70 either via the formation of the metallacyclopentadiene intermediate 68
followed by an intramolecular coupling with the acac ligand (path (a)), or via a stepwise
d

alkyne carbometallation (path (b)). Intermediate 70 would then undergo a stereoselective

te

intramolecular nucleophilic attack of the vinyl moiety onto one of the carbonyl groups to give
the alkoxide complex 71, liberating the cyclohexadienol 72 and regenerating 67 upon reaction
p

with acetylacetone and two alkyne molecules. The final arene product would result from a
ce

facile aromatization of cyclohexadiene 72 by elimination of a water molecule. The related

syn-configuration of acetyl and hydroxy groups in the diene intermediate 72 was confirmed
for isolated product obtained from ethyl 2-fluoroacetoacetate and phenylacetylene (Scheme
Ac

76) [112]. Regarding the formation of 70, it was calculated that both routes are energetically
close for acetylene (R = H) (maximal Ea 18.1 and 17.5 kcal mol–1 for path (a) and (b),
respectively), but route (b) is favored by 5.4 kcal mol–1, and 6.5 kcal mol–1 in the case of
PhCCH, and MeCCH, respectively. Finally, it was also calculated that the nucleophilic
attack of the vinyl group on the second alkyne molecule to form 70 via route (b) proceeds
more easily at the terminal carbon atom than at the internal one. The calculated differences of
the activation energies for PhCCH (5.8 kcal mol–1) and MeCCH (1.9 kcal mol–1) are fully
consistent with the regioselectivities experimentally observed for aromatic and aliphatic
alkynes.

80
Page 80 of 152
Edited June 30

O O
R R (CO) 5 MnBr + + 2R H

HO

O O 3 CO HBr

H
R R R
72
OC O

t
Mn

ip
O O
O
CO
R 67 ( b)
+

cr
2R H
( a)
R

us
R
OC O OC O OC
R O
Mn Mn Mn

an
OC O O O
H R CO CO
71 R
68 R 69
M
Ph ( a)
R ( b)
HO

EtO2C R
d

F O
Ph Mn
te

OC O
isolated CO
70
p

Scheme 79. Proposed mechanism for Mn-catalyzed [2+2+2] cycloaddition of terminal

ce

alkynes with acetylacetone [112]

Ac

Importantly, the presence of a methyl substituent in the active methylene moiety of the
-ketoester changes dramatically the reaction outcome as 2-pyranones are isolated in good
yields instead of tetra-substituted arenes (Scheme 80) [111, 113, 114]. The reaction is quite
efficient for aryl- and alkenyl-substituted terminal alkynes, but rather sluggish in the case
alkyl-substituted derivatives.

81
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Edited June 30

O O 5% (CO) 5MnBr, neat, RT, 24 h O

+ R H
then 10% Bu 4NF toluene 50 °C, 2 h
OEt 1.2 eq R

R Ph p-An p-CF3 C 6H 4 Dec

Other examples:
96% 97% 75% 13%

t
O O

ip
O O

cr
Ph Ph

68% 98%

us
Scheme 80. Synthesis of 2-pyranones using Mn-catalyzed reaction between terminal alkynes
and -ketoesters [111, 113, 114]

an
The proposed catalytic cycle (Scheme 81) begins with complex 73 bearing both the
coordinated alkyne and enol form of the -ketoester. It then rearranges intramolecularly into
M
the metallacyclopentene intermediate 74, which undergoes a reductive elimination liberating
cyclobutenol 75 and regenerating 73 upon reaction with ketoester and alkyne molecules. The
d

resulting cyclobutenol 75 undergoes a ring opening rearrangement into the -ketoester 77,
te

followed by a sequence of base-catalyzed migration of the double bond, deprotonation of the

resulting isomeric -ketoester 78, and intramolecular cyclization of the enolate [79]– to afford
p

final 2-pyranone.
ce
Ac

82
Page 82 of 152
Edited June 30

O O
O O (CO) 5MnBr + + R H
EtO EtO OEt
H+
O O

R R 2 CO HBr
78 [79]

t
H+ EtO

ip
OC O OEt
O Mn
EtO O
OC
O

cr
CO
O OH
73
R
77 R

us
R
R CO OEt

OH OC Mn O

an
EtO OEt
O CO O H
O O
R 74
H
M
76
75 O O
+ R H
OEt
d

Scheme 81. Proposed mechanism for Mn-catalyzed formation of 2-pyranones from -

te

ketoesters and terminal alkynes [114]

p

A conceptually similar Mn-catalyzed formation of the medium-sized cyclic 1,5-

ce

dicarbonyl derivatives was reported by Kinunobu, Takai and coll. (Scheme 82). It was
obtained via formal insertion of a terminal alkyne into the C–C bond of cyclic 1,3-dicarbonyl
Ac

compounds [115]. The reaction is particularly efficient for the combination -ketoesters and
electron-rich aryl and alkenyl acetylenes, and much less for the combination of 1,3-diketones
and other types of alkynes.

83
Page 83 of 152
Edited June 30

O
O
CO2 Et R
5% (CO) 5MnBr
+ R H
neat conditions, 80 °C, 24 h
1.2 eq CO2 Et

R Ph p-Tol p-An p-BrC 6H 4 p-CF 3 C6 H 4

t
Other examples: 84% 94% 95% 8% 18%

ip
O O O

cr
Ph
O

us
CO2 Et CO2 Et CO2 Et

22% 99% 23%

an
O O O
Ph Ph
Ph
M
n CO2Et
n CO2Et
O
n = 1 23% 88% n = 1 93%
d
n = 2 39% n = 2 87%
n = 3 23%
te

Scheme 82. Mn-catalyzed synthesis of medium-sized cyclic -ketoesters [115]

p
ce

The Mn-catalyzed coupling of a terminal alkyne with two molecules of isocyanate gives
the corresponding hydantoin derivatives in a stereoselective manner and in excellent yields,
except for acetylenes bearing primary alkyl substituents (Scheme 83) [116]. The scope of
Ac

isocyanates is much narrower as only aromatic and secondary aliphatic derivatives could be
successfully engaged in the reaction. Other isocyanates R–N=C=O are unreactive (R = TMS,
Tos), or afford isocyanurates cyclotrimerization products instead of hydantoines (R = n-
C18H37, Ph(Me)CH, 1-Ad).

84
Page 84 of 152
Edited June 30

O
Ph Ph
5% (CO) 5 MnBr N N
R H + Ph N C O
dioxane, 150 °C, 24 h
2.2 eq R O

R H Me OMe Cl Br CF3

t
Other examples: 91% 79% 77% 88% 89% 93%

ip
O O O

cr
R R Ph Ph R R
N N N N N N

Ph O O R O

us
R p-Tol p-An p-CF3C 6H 4 Cy 65% R Dec Cy BnOCH 2
91% 93% 94% 84% 32% 80% 15%

an
Scheme 83. Mn-catalyzed synthesis of hydantoines from terminal alkynes and isocyanates
[116]
M
The proposed catalytic cycle (Scheme 84) starts with an oxidative addition of the
d

coordinated alkyne to the metal to give the σ-alkynylhydride complex 81, which undergoes
further insertion of two molecules of isocyanate to give the amidohydride intermediate 83.
te

The latter undergoes a reductive elimination, followed by an intramolecular nucleophilic

attack of the amine group onto the η2-alkyne ligand. This gives the σ-vinyl complex 85
p

stabilized by the chelation of the adjacent carbonyl group, thus providing the adequate
ce

conformation for a stereoselective release of the product formed upon protonation of the Mn–
C bond.
Ac

85
Page 85 of 152
Edited June 30

(CO) 5 MnBr + R H
O

R' R' CO
N N

R O
R
OC CO R
R H
Mn

t
ip
OC Br
O CO
R' OC H
80 Mn
N

cr
H N R' OC Br
R CO

OC O 81

us
Mn
R'NCO
OC Br
CO
85

an
R

R' O
N
M
R'
H N O
N R' OC H
R Mn
OC O OC Br
O
d

Mn R' CO
N
OC Br R 82
te

CO R'
N O
84 OC H R'NCO
Mn
p

OC Br
CO
ce

83

Scheme 84. Proposed catalytic cycle for the Mn-catalyzed synthesis of hydantoines [116]
Ac

Manganese tetraphenylporphyrin complexes can be used for the high temperature

cycloisomerization of enynes in synthetically useful yields and with good functional group
tolerance (Scheme 85) [117]. The selectivity is highly dependent of the nature of the counter
anion. Indeed, BARF or SbF6– anions typically lead to preferential formation of six-
membered products, whereas the more coordinating triflate-anion affords the corresponding
five-membered isomers.

86
Page 86 of 152
Edited June 30

R N 10% [(TPP)Mn]X (A , B , or C )
R N + R N
xylene, 160 °C, 24 h

R= Tos 75% (A ), 61% ( B) 21% ( A), 30% (B ), 95% ( C)

t
[(TPP)Mn]X
R= Ns 71% (A), 38% (B) 19% (A), 36% (B), 81% (C)

ip
R= MesSO2 23% ( A), 38% (B ) 44% (A ), 60% ( B ), 90% (C )
Ph Ph
R= Ph 52% (A ), 57% ( B), 90% (C )
N

cr
N Mn N X

us
Ph Ph

X = BARF (A), SbF6 (B), OTf (C)

Other examples:

Tos N Tos N
H
an
Tos N
H Tos N
H
M
R
H
H H
R Ph p-An p-FC 6H 4
21% ( A ), 26% (B ), 96% ( C ) 67% ( A ), 60% (B ) 31% ( A ), 62% (B ) B 84% 94% 95%
d

Scheme 85. Mn-catalyzed cycloisomerization of enynes [117]

te

The reaction is supposed to proceed via a classic intramolecular nucleophilic addition of

p

the internal olefin moiety to the activated η2-alkyne ligand in [86]+ either at the internal (path
ce

(a)), or at the terminal carbon atom (path (b)) to give isomeric carbocationic intermediates
[87]+ or [88]+, respectively (Scheme 86) [117]. From [87]+, a direct proton shift leads to the
Ac

five-membered diene with concomitant regeneration of starting porphyrine complex. From

[88]+, an insertion of the carbocation into the vicinal C–H bond gives the carbene complex
[89]+, from which the target six-membered product is liberated upon subsequent carbene-
alkene rearrangement.

87
Page 87 of 152
Edited June 30

Mn(TPP) R N
R N

R N

t
Mn(TPP)

ip
Mn(TPP)

Mn(TPP)

cr
R N R N R N

[89]+ [87]+ [86]+

us
Mn(TPP)

an
N
M
[ 88 ]+

Scheme 86. Proposed catalytic cycle for Mn-catalyzed cycloisomerization of enynes [117]
d
te

6. Mn-catalyzed C–H bond activation processes

The first catalytic C–H activation reaction based on an organometallic manganese
p

complex was published by Hartwig and coll. in 1999. It consists in a borylation of pentane
and benzene with PinB–BPin promoted by Cp’Mn(CO)3 (10%) at RT under UV irradiation
ce

and in the presence of CO (2 atm) to give PentBPin, and PhBPin in 36%, and 76% yield,
respectively [118]. Though the recorded catalytic activity was lower than that observed with
Ac

the rhenium analogues CpRe(CO)3 or Cp*Re(CO)3, the Mn-based procedure displayed the
same selectivity regarding the functionalization of the terminal methyl groups of pentane.
Later on, Kuninobu, Takai and coll. reported the catalytic C–H activation of phenyl and
alkenyl moieties bearing a directing nitrogen donor group, in the presence of an aldehyde and
a tertiary silane (Scheme 87) [6, 119]. Good to excellent yields of silyl ethers were obtained
using imidazole or imidazoline moiety as directing groups, providing a reasonable
diastereoselectivity level when optically active imidazoline auxiliaries were used.
Interestingly, whereas Mn2(CO)10 and (CO)5MnMe exhibited the same efficiency as
(CO)5MnBr, other pre-catalysts such as MnCl2 or Mn(acac)3, remained totally inactive, as are

88
Page 88 of 152
Edited June 30

also the rhenium analogue (CO)5ReBr, and a number of ruthenium, rhodium or iridium pre-
catalysts.

N N N N
5% (CO) 5 MnBr OSiEt3
+ RCHO + Et3SiH

t
toluene, 115 °C, 24 h
2 eq 2 eq

ip
R

cr
R Ph o-Tol p-An Oct a Cya
93% 59% 87% 75% 56%

us
Other examples:

N N N N N N
OSiEt3 OSiEt 3 OSiEt 3

CF3 an O S
M
87% 66% 48%

R
d

N N N N N N N N
OSiEt 3 OSiEt3 OSiEt3 OSiEt3
te

Ph Ph Oct Ph
p

72% 68% (de 38%) 46%

ce

R Ph Bn i-Pr
60% 72% 80%
de 60% 30% 95%
Ac

Scheme 87. Mn-catalyzed synthesis of silyl ethers by the direct insertion of the aldehydes into
a C–H bond (a - reaction carried out at 135 °C) [6, 119]

The mechanistic proposal given by the authors involves the formation of a Mn(III)
alkylhydride species via a direct oxidative addition across the ortho-C–H bond of the phenyl
group, followed by an insertion of the aldehyde into the Mn–C bond, and a subsequent
reaction of the resulting Mn(III) alkoxide with triethylsilane to give the silyl ether product and
dihydrogen [6]. However, based on related transformations that appeared more recently (vide
infra), we propose an alternate mechanism involving Mn(I) intermediates only could also be
89
Page 89 of 152
Edited June 30

considered (Scheme 88). The catalytic cycle could actually start with the formation of the
stable metallacycle 90, which could undergo insertion of the aldehyde into the metal-aryl
bond to form the Mn(I) alkoxide 92 via 91. Subsequent coordination of the silane molecule
followed by an elimination of the silyl ether product from 93 and its replacement by an
incoming imidazole substrate molecule would provide the hydride intermediate 94, from
which the metallacycle 90 would be regenerated through an ortho-metallation / elimination of

t
ip
dihydrogen sequence.

cr
N N CO
OC CO

us
+ Mn
OC Br
CO

an
CO HBr

CO
M
N N CO RCHO
H2 Mn
CO
CO
CO
d

90
CO CO
N N N N
te

CO CO
Mn Mn
CO N N CO
H OSiEt3 O
p

94
R 91 R
ce
Ac

N N
N CO N CO
N CO N
Mn Mn CO
O CO O
CO
H SiEt3
Et3SiH
R R
93 92

Scheme 88. Our proposed catalytic cycle for the Mn-catalyzed synthesis of silyl ethers via C–
H activation

90
Page 90 of 152
Edited June 30

More recently it was shown that (CO)5MnBr is prone to induce the highly selective
insertion of terminal alkynes into the C–H bond of ortho-phenylpyridines, in the presence of
the bulky amine base Cy2NH (Scheme 89) [7]. It has to be pointed out that terminal alkynes
are considered as tricky reaction partners in C–H alkenylation due to their tendency to
undergo competitive cyclo-trimerization. Here, the reaction shows a remarkable application
scope and provides alkene products in moderate to good yield with an excellent chemo- and

t
ip
stereoselectivity, namely the selective activation of one type of C–H bond only with the
exclusive formation of anti-Markovnikov product with a E-configuration of the alkenyl

cr
moiety. When two ortho C–H bonds are available typically the less hindered one gets
activated selectively.

us
an
M
d
p te
ce
Ac

91
Page 91 of 152
Edited June 30

(2 eq)
N N R
10% (CO) 5 MnBr, 20% Cy2 NH
+ Et2 O, 80-100 °C, 6-12 h

R H

R H Me OMe F Cl Br I CF3 NO2 CO2 Me

t
76% 71% 63% 82% 79% 79% 74% 71% 48% 66%

ip
Other examples:

cr
R
N

us
N
2-Py
Ph R
o-Tol

R 3-Me 5-Me 4-OMe 5-Ph 5-CO 2Et

68% 82% 75% 80% 71%
77%

an R o-Tol m-Tol 2-Naph o-C 6H 4CF3 2-thienyl

80% 75% 78% 65% 51%
M
2-Py
2-Py
o-Tol 2-Py R
d
o-Tol
te

R (CH2 )3 Cl OCOPh CH2 OCOPh

75% 86%
68% 48% 46%
p

F N
2-Py N 2-Py
ce

o-Tol F
S

27% 51% 51%

Ac

2-Py 2-Py 2-Py

R o-Tol o-Tol
R Ph o-Tol
60% 71% +
F MeO MeO
67%, 1:2 mixture

Scheme 89. Mn-catalyzed aromatic C–H bond alkenylation with terminal alkynes [7]

92
Page 92 of 152
Edited June 30

The proposed catalytic cycle, based on detailed mechanistic experiments and supported
with DFT calculations, is shown in Scheme 90. Complex 95 formed by an initial base-assisted
intramolecular C–H activation process undergoes coordination of an alkyne molecule, which
experiences an insertion into the Mn–C bond to form the seven-membered metallocyclic
intermediate complex 97. The authors tentatively attributed the observed high chemo- and
stereoselectivity of the reaction to the hindered geometry of both intermediates 97 and 98. The

t
ip
latter then undergoes a coordination of a second alkyne molecule, allowing a ligand to ligand
proton transfer (confirmed by isotope labeling experiments) leading to the σ-alkynyl

cr
intermediate 99. The substitution of the product molecule by an incoming phenylpyridine
substrate, followed by an alkynyl ligand-assisted C–H activation leads to the η2-alkyne

us
complex 96, thereby closing the catalytic cycle.

an
CO CO
N N
OC CO CO
+ Mn + Cy2 NH Mn + CO + [Cy2 NH2]Br
M
Br CO CO
CO CO
95
R
d

2 CO
te

CO
N
p

CO
Mn
ce

CO CO
N
CO R
Mn
N 96
CO
Ac

R N CO
CO
R Mn
100 CO

97 R
N
R
N CO
N CO
CO
CO
Mn
Mn
CO
CO
R R R
R 99 98

93
Page 93 of 152
Edited June 30

Scheme 90. Proposed catalytic cycle for Mn-catalyzed aromatic C–H bond alkenylation [7]

A conceptually similar insertion of acrylic esters or vinylketones across an aromatic C–

H bond was developed late on (Scheme 91) [9]. As in the previous case, the reaction exhibits
both an excellent functional group tolerance and a high level of chemoselectivity towards the
single activation of the less hindered C–H bond.

t
ip
cr
N N
10% (CO) 5MnBr, 20% Cy2 NH
1.5 eq + CO2Me
Et2 O, 100 °C, 12 h CO2Me

us
R R

an
R H Me OMe F Cl
85% 73% 63% 77% 75% 68% 74% 65%
Br I CF3
M
Other examples:

2-Py 2-Py
R
d

N CO2Me CO2Me
te

CO2Me
49% 75%
p

R 3-Me 5-Me 4-OMe 5-CO2 Et

ce

41% 82% 80% 66%

N N N N
2-Py O
Ac

N CO2Me
Bu CO2Me
O
Et
88% 32% 41%

2-Py O 2-Py 2-Py

R S CO2 Me O

35% 40%
R Et Ph OEt OBu OPr-i OBu-t OBn OPh
58% 57% 82% 78% 87% 66% 85% 75%

94
Page 94 of 152
Edited June 30

Scheme 91. Mn-catalyzed aromatic C–H bond conjugate addition to α,-unsaturated ketones
and esters [9]

The proposed reaction mechanism based on DFT calculations (Scheme 92) includes
again the initial formation of the metallacycle 95, followed by the chelating coordination of

t
the acrylate molecule to form complex 101, which then undergoes an insertion into the Mn–C

ip
bond to afford the manganese enolate complex 102. Importantly, the presence of a carbonyl
moiety appears to be crucial for the insertion step to occur, probably due to the stabilization of

cr
the -alkene complex 101. Experimentally, the reaction fails for styrene derivatives lacking
such a chelating coordination. A protonation of 102 leads to the still coordinated final

us
product, which is finally displaced by incoming phenylpyridine and acrylate substrates,
closing a catalytic cycle by base-assisted C–H activation in the resulting intermediate [104]+.

an
M
d
p te
ce
Ac

95
Page 95 of 152
Edited June 30

CO CO
N N
OC CO CO
+ Mn + Cy2NH Mn + CO + [Cy2NH2]Br
Br CO CO
CO CO
95
OR

t
ip
O

2 CO

cr
CO
N
CO
Mn

us
O

OR
101

an
CO CO
N N
CO CO
Mn Mn
O O
M
OR
[104 ]+ 102 OR
d

N
[Cy2NH2 ]Br
te

CO2 R
N CO
CO
Mn Cy 2NH
p

OR O
+
ce

N O
[103 ]+ OR
Ac

Scheme 92. Proposed catalytic cycle for Mn-catalyzed aromatic C–H bond conjugate addition
[9]
The imine moiety also constitutes a suitable directing group for Mn-catalyzed aromatic
C–H activation in the presence of alkynes, providing a direct and efficient route to a wide
variety of substituted isoquinolines (Scheme 93) [8]. Noticeably, this transformation
represents the first transition metal-catalyzed synthesis of isoquinolines under oxidant-free
conditions generating only hydrogen and small amounts of alkenes as side products. Both
internal and terminal alkynes bearing various types of functional groups can be engaged in

96
Page 96 of 152
Edited June 30

this reaction, providing in the latter case the formation of single regioisomers of the final
products.
The proposed catalytic cycle (Scheme 94) includes an initial intramolecular aromatic
C–H bond activation assisted by imine molecule as a base, followed by the coordination and
insertion of the alkyne molecule to give the metallacyclic intermediate 107. The latter
undergoes an elimination to afford the final isoquinoline and the intermediate hydride

t
ip
complex 108, which transforms into the starting metallacycle 105 by a sequence of imine
coordination and hydride-assisted C–H activation with concomitant hydrogen elimination.

cr
Alternatively, the regeneration of 105 from 108 can also be seen as the result of an alkyne
molecule coordination and insertion across the Mn–H bond, and similar σ-vinyl ligand

us
assisted C–H activation of the imine molecule, eventually giving Z-alkene as a side product as
detected in small amount in the reaction mixture.

an
M
d
p te
ce
Ac

97
Page 97 of 152
Edited June 30

p-An
p-An
NH
10% (CO) 5 MnBr N
MeO dioxane, 105 °C, 12 h
+ MeO R

R R R

1.5 eq R Ph p-An 1-Naph p-FC 6H 4 p-ClC 6H 4 p-CF 3C 6H 4 Pr

t
89% 82% 92% 79% 88% 79% 73%

ip
R' Other examples:
F

cr
N

us
R Ph
Ph F
Ph
N
R H H H Me t-Bu t-Bu Ph F SMe Ph
75%

an
R' Bu s-Bu i-Pr Bu OMe NMe2 Bu Bu Bu
86% 87% 82% 93% 93% 97% 77% 88% 58%

p-An Bu Bu
M
R
N N N
+
MeO R Ph Ph
d

Ph R Ph
R Bu TMS 2-thienyl cyclopropyl
te

74% 88% 45% 56% R = Me 79% 9%

R = OMe 24% 59%
R Ph 4-t-BuC 6 H4 p-BrC 6H 4 p-MeCO 2C 6H 4 R =F 23% 63%
p

87% 85% 53% 63% R = CF3 58% 0%

ce

t-Bu Bu F Bu
Cl
N N N
Ac

Me2 N Ph Ph

N Ph Ph
73% Boc 48% 75%

p-An p-An p-An

N N N
Et
MeO p-An MeO p-An MeO TMS
OH Bu Ph
53% 94% (9.2:1 isomers ratio) 96% (1:1.7 isomers ratio)

98
Page 98 of 152
Edited June 30

Scheme 93. Mn-catalyzed dehydrogenative annulation of imines with alkynes via C–H/N–H
bonds activation [8]
2 Ph2C=NH + (CO) 5MnBr

CO [Ph2 C=NH2 ]Br

R R

t
H CO H CO

ip
Ph N Ph N R R
CO CO
Mn Mn
OC CO CO

cr
R CO
H2
R 105
H CO

us
112 Ph N
CO
CO H CO Mn
Ph N
CO CO CO
OC Mn Mn R R

an
CO OC CO
H 106
R
109
R 111
M
CO CO H CO
Ph N
OC CO CO CO
R Mn OC Mn Mn
d
CO CO CO
H H
R R
108
te

R
110 107
Ph
p

N
ce

R
R

Scheme 94. Proposed catalytic cycle for Mn-catalyzed dehydrogenative annulation of imines
Ac

with alkynes [8]

Very recently, Ackermann and coll. reported the one-step assembly of highly valuable
derivatives of cyclic -aminoacids upon coupling of N-aryl-substituted imines with acrylates
(Scheme 95) [10]. Contrary to most of the examples discussed above, the reaction is more
efficiently catalyzed by Mn2(CO)10, than by (CO)5MnBr. It tolerates numerous functional
groups and shows an excellent cis-selectivity providing a full control of up to three

99
Page 99 of 152
Edited June 30

contiguous stereocenters. Noticeably, the reaction can even be carried out in air, with a slight
decrease only of the product yield.
p-An
N NHp-An
5-10% Mn 2(CO) 10
+ CO2 Et CO2Et
DCE or toluene, 120 °C, 18 h
R

t
R 2 eq

ip
R H Me Ph F Cl Br
97% 94% 75% 75% 67% 68%
Other examples:

cr
R NHp-An
NHp-An NHp-An

us
CO2 R CO2Et CO2Et

82% (5:1 regioisomers ratio)

R Et Ph Cy

an
R Bu Bn All
89% 88% 67% 85% 85% 87%

F
M
NHR NHp-An

CO2Et CO2Et
NHp-An
d
O
CO2Et O
R Ph p-FC 6H 4 80%
te

92% 80% F
73%
p

NHp-An p-Tol
NHp-An NHp-An
ce

CO2 Et CO2Et
CO2 Et

72%
74% (4:1 regioisomers ratio) 64%
Ac

Scheme 95. Mn-catalyzed synthesis of cyclic -aminoesters from ketimines and acrylates
[10]

The proposed catalytic cycle (Scheme 96) involves the formation of a cationic Mn(I)
complex, [113]+, which undergoes a weak base assisted C–H metallation. Subsequent
substitution of a carbonyl ligand for an acrylate molecule, followed by its insertion into the
Mn–C(aryl) bond gives the enolate intermediate 115. The latter undergoes an intramolecular
nucleophilic attack of enolate moiety to the electrophilic imine carbon atom, followed by a

100
Page 100 of 152
Edited June 30

protonation of the resulting amide and regeneration the active species [113]+ upon
coordination of another imine molecule.

NPh
+ Mn2(CO) 10
Ph
NHPh

t
(CO) 5Mn

ip
CO2R NPh
Ph
CO Ph NHPh

cr
R' N CO + CO
NHPh Mn Ph
CO +
OC CO
Ph CO

us
[113]+
CO Ph
OC CO

an
CO
Ph Mn N
CO
N CO Mn
O
CO
CO
M
OR
Ph 114
R'
N CO
116 CO
d
Mn
R' OR
CO O
te

CO O
CO
R' OR
115
p
ce

Scheme 96. Proposed catalytic cycle for the Mn-catalyzed synthesis of cyclic -aminoesters
via aromatic C–H activation of N-aryl ketimines in the presence of acrylates [10]
Ac

7. Reduction of C=O double bond

7.1. Hydrosilylation of aldehydes and ketones
Though the first example of Mn-catalyzed ketone hydrosilylation was reported by Yates
in 1982 [120] (Table 5, entry 62), a real breakthrough in this field was achieved a decade later
with the findings of Cutler and coll. on the autocatalytic hydrosilylation of σ-acyl manganese
complexes 47a-b (Table 5) [121, 127], and on the hydrosilylation of Fp-substituted ketones
using the latter σ-acyl manganese complexes as pre-catalysts (Table 5, entries 75-86) [122].

101
Page 101 of 152
 t
ip
Edited June 30

cr
Table 5. Mn-catalyzed hydrosilylation of aldehydes and ketones [12-14, 120-126]

us
CO
OC CO Mes

an
Mn Mn
R N
CO Mn Mn OC
L BF4 OC
O OC CO OC CO N
OC OC

M
Mes
L = CO, R = Me 47a
L = CO, R = Ph 47b 117 [ 118 ]+ 119
L = PPh3 , R = Ph 47c

N N ed
N
N
PPh2
N
PPh 2
pt
Mn
N Mn N Mn H
t-Bu O O Bu-t
PPh2 PPh 2
ce

N N
Bu-t t-Bu

120 121 122

Ac

Catalyst TOF
Entry Substrate Silane (eq.) Conditions Products (yield, %) TON Ref.
(mol %) (h–1)

1 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 1 h PhCH2OH (90)a 90 90 [13]
PhCHO
2 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 0.33 h PhCH2OH (95)b 190 570 [12]

102

Page 102 of 152

 t
ip
Edited June 30

cr
3 p-AnCHO 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 2.8 h p-AnCH2OH (90)b 180 64.3 [12]

us
4 p-Me2NC6H4CHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 1 h p-Me2NC6H4CH2OH (90)a 90 90 [13]

5 p-PhCCC6H4CHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 1 h p-PhCCC6H4CH2OH (88)a 88 88 [13]

an
6 p-ClC6H4CHO 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 0.3 h p-ClC6H4CH2OH (87)b 174 580 [12]

7 m-FC6H4CHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 8 h m-FC6H4CH2OH (90)a 90 11.3 [13]

M
8 p-NO2C6H4CHO 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 1 min p-NO2C6H4CH2OH (73)b 146 8800 [12]

9 p-CNC6H4CHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 1 h p-CNC6H4CH2OH (89)a 89 89 [13]

ed
10 p-EtCO2C6H4CHO 119 (1) Ph2SiH2 (1.05) toluene, UV, RT, 8 h p-EtCO2C6H4CH2OH (55)a 55 6.9 [13]

11 p-MeCOC6H4CHO 119 (1) Ph2SiH2 (1.05) toluene, UV, RT, 8 h p-MeCOC6H4CH2OH (51)a,c 51 6.4 [13]
pt
12 2-PyCHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 1 h 2-PyCH2OSiHPh2 (97)d 97 97 [13]

13 2-furylCHO 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 8 h 2-furylCH2OSiHPh2 (97)d 97 12.1 [13]
ce

14 N 119 (1) Ph2SiH2 (1.05) toluene, UV, RT, 1 h N 54 54 [13]

CHO
(54)
Ac

OH

15 Ph
CHO 119 (1) Ph2SiH2 (1.05) toluene, UV, RT, 8 h Ph OH (80) 80 10 [13]

16 CHO 119 (1) Ph2SiH2 (1.05) toluene, UV, RT, 8 h 71 8.9 [13]
7 7 OH (71)

103

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cr
CHO
17 119 (1) Ph2SiH2 (2.5) toluene, UV, RT, 8 h OH (70) 70 8.8 [13]

us
18 47c (2.4) PhMe2SiH (1.1) C6D6, RT, ˂ 4 min Ph(Me)CHOSiMe2Ph (95) 40 600 [123]
19 47c (2.4) Ph2SiH2 (1.1) C6D6, RT, ˂ 4 min Ph(Me)CHOSiHPh2 (>95)d 40 600 [123]

an
20 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 3 h Ph(Me)CHOSiHPh2 (>99)d 20 6.7 [124]
21 [118]+ (0.5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h Ph(Me)CHOSiMe2Ph (99)d 200 100 [125]

M
22 [118]+ (5) Et3SiH (1.5) CH2Cl2, RT, 5 h Ph(Me)CHOSiEt3 (95)d 19 3.8 [125]
+ d
23 [118] (5) Ph2SiH2 (1.5) CH2Cl2, RT, 0.5 h Ph(Me)CHOSiHPh2 (>99) 20 40 [125]
a
24 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h Ph(Me)CHOH (65) 65 16.2 [13]

ed
b
25 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 2 h Ph(Me)CHOH (91) 182 91 [12]
PhCOMe
26 121 (0.1) PhSiH3 (1) C6D6, RT, 4 min (Ph(Me)CHO)2SiHPhi (99)d 1000 15000 [14]
27 121 (0.33) PhSiH3 (0.33) C6D6, RT, 6.5 h (Ph(Me)CHO)3SiPh (99)d 330 50.7 [14]
pt
28 122 (0.1) PhSiH3 (1) C6D6, RT, 4 min (Ph(Me)CHO)2SiHPh (87)d 870 13000 [126]
ce

29 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 3 h p-Tol(Me)CHOSiHPh2 (>99)d 20 6.7 [124]
p-TolCOMe
30 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h p-Tol(Me)CHOH (92)a 92 23 [13]

o-Tol(Me)CHOH (95)a
Ac

31 o-TolCOMe 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 24 h 95 4 [13]

32 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 7 h p-An(Me)CHOSiHPh2 (28)d 5.6 0.8 [124]
+ d
33 [118] (5) PhMe2SiH (1.5) CH2Cl2, RT, 0.8 h p-An(Me)CHOSiMe2Ph (>99) 20 25 [125]
p-AnCOMe a
34 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h p-An(Me)CHOH (97) 97 24.2 [13]
35 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 2.3 h p-An(Me)CHOH (86)b 172 75 [12]
i d

104

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cr
36 121 (1) PhSiH3 (1) C6D6, RT, 25 min (p-An(Me)CHO)2SiHPhi (>99)d 100 240 [14]

(Mes(Me)CHO)2SiHPh (80)d

us
37 MesCOMe 121 (1) PhSiH3 (1) C6D6, RT, 120 h 80 0.65 [14]

38 Me 2N 121 (1) PhSiH3 (1) C6D6, RT, 6 h (Ar(Me)CHO)2SiHPh (>99)d 100 16.7 [14]

an
O

39 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h p-FC6H4(Me)CHOH (83)a 83 20.7 [13]
F
i d
40 121 (1) PhSiH3 (1) C6D6, RT, 4 h (Ar(Me)CHO)2SiHPh (>99) 99 25 [14]

M
O

41 Cl 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h p-ClC6H4(Me)CHOH (0)a 0 0 [13]
O

42
43
Br
O
117 (5)
119 (1) ed
Ph2SiH2 (1.5)
Ph2SiH2 (1.5)
CH2Cl2, RT, 7 h
toluene, UV, RT, 4 h
p-BrC6H4(Me)CHOSiHPh2 (99)d
p-BrC6H4(Me)CHOH (0)a
99
0
14.3
0
[124]
[11]
pt
44 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 18 h Ar(Me)CHOSiHPh2 (0)d 0 0 [124]
+ d
45 O 2N [118] (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h Ar(Me)CHOSiMe2Ph (18) 3.6 1.8 [125]
ce

O b
46 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 3 h p-NO2C6H4(Me)CHOH (58) 116 38.6 [12]

47 C6F5COMe 121 (1) PhSiH3 (1) C6D6, RT, 3.5 h (Ar(Me)CHO)2SiHPhi (>99)d 100 28.5 [14]
Ac

48 PhCOCF3 121 (1) PhSiH3 (1) C6D6, RT, 12 h (Ph(CF3)CHO)3SiPh (99)d 100 8.3 [14]

49 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 18 h 1-Naph(Me)CHOSiHPh2 (0)d 0 0 [124]

1-NaphCOMe
50 [118]+ (5) PhMe2SiH (1.5) CH2Cl2, RT, 18 h 1-Naph(Me)CHOSiMe2Ph (35)d 7 0.4 [125]

51 2-NaphCOMe 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 3 h 2-Naph(Me)CHOSiHPh2 (99)d 20 6.7 [124]
+ d

105

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cr
52 [118]+ (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h 2-Naph(Me)CHOSiMe2Ph (99)d 20 10 [125]
53 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h 2-Naph(Me)CHOH (96)a 96 24 [13]

us
54 FcCOMe 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 24 h Fc(Me)CHOH (75)a 75 3.1 [13]

an
OH

55 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 1.5 h 128 85.3 [12]
(64%)b

M
O OH

56 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 24 h 57 2.4 [13]

(57%)a

57
Ph
O
120 (0.5) ed
PhSiH3 (0.5) MeCN, 80 °C, 2 h (Ph(C3H5)CHO)2SiHPh (>98%)d 196 98 [12]
pt
58 [118]+ (5) PhMe2SiH (1.5) CH2Cl2, RT, 18 h (Ph2CHO)SiMe2Ph (15%)d 3 0.15 [125]
ce

59 Ph2CO 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 2 h Ph2CHOH (73%)b 146 73 [12]
i d
60 121 (1) PhSiH3 (1) C6D6, RT, 20 min (Ph2CHO)2SiHPh (>99%) 100 303 [14]
Ac

O O
61 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 3 h (45%) b 90 30 [12]
Ph Ph Ph Ph

62 Mn2(CO)10e Et3SiH (1) neat, UV, 29 °C, 20 h Me2CHOSiEt3 (5%)g 700 35 [120]
63 MeCOMe 47c (2.4) PhMe2SiH (1.1) C6D6, RT, ˂ 4 min Me2CHOSiMe2Ph (>95%)d 40 600 [123]
64 47c (2.4) Ph2SiH2 (1.1) C6D6, RT, ˂ 4 min Me2CHOSiHPh2 (>95%)d 40 600 [123]

106

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cr
65 117 (5) Ph2SiH2 (1.5) CH2Cl2, RT, 3 h Pr(Me)CHOSiHPh2 (>99%)d 20 6.7 [124]
PrCOMe d

us
+
66 [118] (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h Pr(Me)CHOSiMe2Ph (>99%) 20 10 [125]

67 121 (0.01) PhSiH3 (1) neat, RT, 5 min (Bu(Me)CHO)2SiHPh (62%) 6200 74400 [14]
BuCOMe
68 121 (0.33) PhSiH3 (0.33) C6D6, RT, 24 h (Bu(Me)CHO)2SiHPh (74%) 244 10.2 [14]

an
69 OctCOMe 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 24 h Oct(Me)CHOH (93%)a 93 3.9 [11]

M
70 [118]+ (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h Pr(Me)CHOSiMe2Ph (>99%)d 20 10 [125]

Bn(Me)CHOH (78%)b

ed
71 BnCOMe 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 1.5 h 156 104 [12]

72 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 4 h BnCH2(Me)CHOH (80%)a 80 20 [13]
BnCH2COMe b
73 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 3.3 h BnCH2(Me)CHOH (80%) 160 48.5 [12]
pt
OH OH
O +
ce

74 119 (1) Ph2SiH2 (1.5) toluene, UV, RT, 24 h Ph Ph 47 2 [13]

Ph
(47%)a (22%)a

75 47a (4.2) Et3SiH (1.25) C6D6, RT, 11 h Fp(Me)CHOSiEt3 (95%) 22.6 2 [122]
Ac

76 47a (4.6) Ph2SiH2 (1.2) C6D6, RT, 4 h (Fp(Me)CHO)2SiPh2j (100%) 21.7 5.4 [122]
77 FpCOMe 47a (3.8) Et2SiH2 (1.25) C6D6, RT, 18 h (Fp(Me)CHO)2SiEt2j (91%) 24 1.3 [122]
78 47a (4.6) PhSiH3 (1.2) C6D6, RT, 8 h (Fp(Me)CHO)2SiHPh (92%) 20 2.5 [122]
79 47b (2.6) Et3SiH (1.1) C6D6, RT, 2 h Fp(Me)CHOSiEt3 (90%) 34.6 17.3 [122]

107

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cr
80 47b (2.6) PhMe2SiH (1.1) C6D6, RT, 1 h Fp(Me)CHOSiMe2Ph (66%) 25.4 25.4 [122]
81 47b (3.3) Ph2SiH2 (1.2) C6D6, RT, 20 min (Fp(Me)CHO)2SiPh2j (85%) 25.7 78 [122]

us
82 47b (2.2) Et2SiH2 (1.25) C6D6, RT, 22 h (Fp(Me)CHO)2SiPh2j (94%) 42.7 2 [122]
83 47c (0.47) Ph2SiH2 (1.1) C6D6, RT, 5 h (Fp(Me)CHO)SiHPh2 (87%) 185 37 [122]

an
84 47a (20.2) Ph2SiH2 (1.3) C6D6, RT, 2 h (Fp(Ph)CHO)SiHPh2 (15%) 0.75 0.4 [122]
85 FpCOMe 47b (2.8) Ph2SiH2 (1.1) C6D6, RT, 20 h (Fp(Ph)CHO)SiHPh2 (30%) 10.7 0.5 [122]
86 47c (2.4) Ph2SiH2 (1.1) C6D6, RT, 0.5 h (Fp(Ph)CHO)SiHPh2 (92%) 38.3 76.6 [122]

M
87 121 (1) PhSiH3 (1) C6D6, RT, 36 min (i-Pr(Me)CHO)SiH2Phk (>99%)d 100 166.7 [14]
i-Pr2CO
88 121 (0.5) PhSiH3 (0.5) C6D6, RT, 42 min (i-Pr(Me)CHO)2SiHPhk (>99%)d 200 286 [14]

89

90
Cy2CO

O
121 (1)

117 (5)
ed
PhSiH3 (1)

Ph2SiH2 (1.5)
C6D6, RT, 24 h

CH2Cl2, RT, 3 h
(Cy(Me)CHO)2SiHPho (>99%)d

C5H11(Me)CHOSiHPh2 (>99%)d
100

20
4.2

6.7
[14]

[124]
pt
91 [118]+ (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h C5H11(Me)CHOSiMe2Ph (>99%)d 20 10 [125]
ce

92 47c (2.4) PhMe2SiH (1.1) C6D6, RT, ˂ 4 min CyOSiMe2Ph (92%) 38.3 575 [123]
d
93 47c (2.4) Ph2SiH2 (1.1) C6D6, RT, ˂ 4 min CyOSiHPh2 (91%) 37.9 569 [123]
d
Ac

+
94 O [118] (5) PhMe2SiH (1.5) CH2Cl2, RT, 2 h CyOSiHPh2 (>99%) 20 10 [125]
95 120 (0.5) PhSiH3 (0.5) MeCN, 80 °C, 2 h (CyO)3SiPh (75%) 150 75 [12]
96 121 (0.01) PhSiH3 (1) neat, RT, 5 min (CyO)2SiHPh (64%) 6400 76800 [14]
97 121 (0.33) PhSiH3 (0.33) C6D6, RT, 4 h (CyO)3SiPh (>99%)d 330 82.5 [14]
98 122 (0.1) PhSiH3 (1) C6D6, RT, 4 min (CyO)2SiHPh (80%)d 800 12000 [126]

108

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cr
O OSiHPh2

us
99 47c (2.4) Ph2SiH2 (1.1) C6D6, RT, 4 h 33.3 8.3 [123]
(80%)

a
Isolated yield after hydrolysis with MeOH/2M NaOHaq

an
b
Isolated yield after desilylation with HCl or Bu4NF
c
ca. 40% of the corresponding diol product detected by 1H NMR in the crude reaction mixture
d1

M
H NMR product yield using internal standard
e
S/C ration of ca. 14000
g
GC product yield

ed
h
90% isolated yield
i
Depending on the R group 12.5-25% of (R(Me)CHO)3SiPh also forms
j
A 1.3:1 to 1:1 mixture of (Fp(Me)CHO)2SiR2 and (Fp(Me)CHO)SiHR2 is obtained
pt
k
10-20% of (i-Pr(Me)CHO)SiH2Ph also forms
ce
Ac

109

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Edited June 30

Importantly, pre-treatment of the manganese σ-acyl complexes 47 with silane at RT

during 20 min resulted in a drastic acceleration of the ketone hydrosilylation process (less
than 4 min vs. 45 min reaction time for acetone hydrosilylation with PhMe2SiH using pre-
catalyst 47c) [123]. The hydrosilylation of FpCOMe with PhSiH3 using catalyst 47a can even
proceed with a subsequent reductive cleavage of the silyl ether intermediates (vide infra) to
afford FpEt (51%) as a major product accompanied with [Fp(Me)CHO]3SiPh (24%), whereas

t
ip
47b and 47c under the same conditions afforded selectively the latter products in 43%, and
82%, respectively [128].

cr
The proposed catalytic cycle (Scheme 97) involves the initial addition of silane to the σ-
acyl ligand, followed by coordination of the silane and subsequent hydrogenolysis of the Mn–

us
C bond to give the 16-electron manganese silyl complex 123. The latter is subsequently
engaged in the uptake of a ketone molecule to form the intermediate 125, which further adds
one silane molecule to form 126, from which liberation of the silyl ether takes place, with
concomitant regeneration of 123.

an
M
CO CO
OC CO OC CO
Mn + R 3 SiH Mn
CO CO
d

L L
O R 3 SiO
te

L = CO, PPh3 R 3SiH

R 3SiOEt + CO
p

R'
R 3 SiO CO R' R'
CO
ce

R' R3 Si Mn
O
CO
L
123
Ac

R 3SiO R' CO
CO R 3 Si CO
R' CO Mn
Mn
R3 Si O CO
CO L
H L R' 124
R'
126

R' CO
CO
R 3 SiH R' Mn
R3 SiO CO
L
125

110
Page 110 of 152
Edited June 30

Scheme 97. Proposed catalytic cycle for the ketone hydrosilylation using manganese σ-acyl
complexes (CO)4(L)MnOAc (L = CO, PPh3) as pre-catalysts [123, 128].

Substitution of one of the CO ligands by PPh3 results in a significant increase in the

catalytic activity of the precatalyst giving TOF of more than 600 h–1 at RT for several
benchmark ketone substrates (entries 18, 19, 63, 64, 92, 93), up to 1600 h–1 for acetone

t
ip
hydrosilylation with PhMe2SiH [123], which could be rationalized in terms of a better
stabilization of the catalytically active species 123 (Scheme 97).

cr
The half-sandwich manganese complexes 117 and [118]+ behave as moderately active
but recyclable catalysts for ketone hydrosilylation at RT (Table 5) [124, 125]. The cationic

us
complex [118]+ is more active than its neutral congener 117, reaching TOF of ca. 100 h–1 for
the hydrosilylation of acetophenone with PhMe2SiH (entry 21). The authors stressed the
possible role of ring slippage as a mechanistic pathway favoring coordination and activation

an
of the silane, a hypothesis consistent with the relative inertness of the parent complex [(η6-
C6H6)Mn(CO)3]BF4 bearing a strongly bound arene ligand.
M
The Mn-catalyzed hydrosilylation of ketones has recently experienced an impressive
renaissance, providing several efficient catalytic systems based on salen [12], NHC [11], and
pyridine diimine [14, 126] ligands. While photochemical or thermal activation is required for
d

complexes 119 and 120 (Table 5), the complexes 121 and 122 based on a pyridine diimine
te

ligand scaffold devoid of pendant phosphine moieties operate at RT with extremely high
reaction rates. TOF up to 74400 h–1, and 76800 h–1 were indeed obtained with 121 for the
p

hydrosilylation of 2-hexenone, and cyclohexenone, respectively, with PhSiH3 (entries 67 and

ce

96) under neat conditions. Even a catalyst loading as low as 0.01% led to a total substrate
conversions within 5 min at RT. To date, this represents the most active catalytic system for
ketone hydrosilylation based on a first row transition metal complex. It is at least 3, 1500, and
Ac

300 times more active than the best reported iron, cobalt, and nickel catalysts, respectively
[14, 31]. The remarkable catalytic activity displayed by 121 allows in particular the
development of an atom-economic ketone hydrosilylation using a reduced amount of PhSiH3
(0.33-0.5 eq) albeit the reactions in these cases are significantly slower (0.6-24 h, entries 27,
68, 88, 97) and require 0.33-0.5% of catalyst [14]. The diamagnetic hydride complex 122
generally shows just a slightly lower catalytic efficiency than the paramagnetic complex 121
giving TOF of 13000 h–1, and 15000 h–1, respectively, for acetophenone reduction under
identical reaction conditions (entries 28 and 26) [126]. Though the authors originally
proposed a non-classical hydrosilylation pathway involving a radical transfer from 121 to the

111
Page 111 of 152
Edited June 30

coordinated ketone [14], the transformation of complex 121 into 122 by a hydrogen
abstraction from silane and subsequent classic hydride-mediated hydrosilylation mechanism
cannot be excluded.
Catalytic systems based on NHC (119) [13] and salen (120) [12] manganese complexes
are far less active than complexes 47c and 121, but offer instead a larger functional group
tolerance. For example, complex 119 promotes the hydrosilylation of various aldehydes

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ip
bearing heterocyclic (entries 12-14), conjugated (entry 15) or non-conjugated (entries 16-17)
alkene, alkyne (entry 5), and amine (entry 4) moieties, as well as other reducible groups such

cr
as nitrile, ester or even ketone (entries 9-11) [13]. Interestingly, the salen complex 120 shows
a high activity in the reduction of p-nitrobenzaldehyde (TOF of ca. 8800 h–1) without any

us
significant destruction of the nitro group (entry 8) [12]. While the hydrosilylation of
conjugated ketone with complex 119 proceeds mostly at the carbonyl group (entry 74), for
complex 120 a conjugated reduction of C=C bond is the major process (entry 61). Both

an
catalytic systems based on the pre-catalysts 119 and 120 show induction periods probably
required for generating the active metal hydride species, further to photochemical CO
M
substitution for 119, or further nitride ligand reduction for 120.
One of the notable advantages of the Mn-based catalysts 47c, 117-122 for ketone
hydrosilylation as compared to noble metal catalysts is the typical negligible formation of
d

dehydrogenative silylation products. Yet, the formation of the corresponding enol ether from
te

cyclohexanone or acetophenone and Et3SiH can be detected in 34% GLC yield (95% and 75%
ketone conversions, respectively) under more forcing conditions (1% Mn2(CO)10, 5% EtI, 5%
p

Et2NH, toluene, 100 °C, 16 h) [129].

ce

Finally, aldehydes and ketones can be reduced by PhSiH3 at RT using the Mn(dpm)3
catalyst in the presence of oxygen (Scheme 98) [130]. The reaction is highly efficient for
cyclic five- and six-membered ketones following generally Felkin model, but, curiously,
Ac

much less for open-chain and macrocyclic substrates. The catalytic cycle includes a
nucleophilic addition of the Mn(V) hydride intermediate (dpm)2(O2)MnH 55 (Scheme 55) to
the carbonyl atom of ketone, followed by the solvolysis of the resulting alkoxide
(dpm)2(O2)MnOCHR2 with i-PrOH, and the regeneration of 55 from (dpm)2(O2)MnOi-Pr
upon reaction with the silane.

112
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Edited June 30

3% Mn(dpm) 3 , 2 eq PhSiH 3, O2 R = Me 84% (cis/trans 1:13)

O R HO R
i-PrOH/DCE 10:1, RT R = t-Bu 98% (cis/trans 1:14)

Other examples:

O OH OH
HO HO HO

t
O Ph Hex Hex

ip
87% (cis/trans 1:2.1) 81% (cis/trans 9:1) 92% 24% 43%

cr
HO

+ O

us
HO O OH

OH OH
85% 99% 58% (exo/endo 1:14) 53% (exo/endo 7:1)

HO HO
an
R
M
OH OH

13% 92%
22% R H OMe NO2
68% 56% 80%
d

OH Oct Oct
te

H H H
p

H H H H H H
HO
ce

HO MeO
H H
47% 92% 61%
Ac

Scheme 98. Mn-catalyzed direct ketone reduction with PhSiH3 [130].

7.2. Hydrosilylation of carboxylic acid derivatives

A highly efficient Mn-catalyzed hydrosilylation of esters under mild conditions (RT,
>30 min for full substrate conversion, Table 6) that operates with the same mechanism than
the one shown in Scheme 97 was reported by Cutler and coll. [131]. As in case of ketone
hydrosilylation, complex 47c is more active than 47a (22 h–1 vs. 132 h–1 TOF for ethylacetate
hydrosilylation under the same conditions).

113
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Edited June 30

cr
Table 6. Mn-catalyzed hydrosilylation of esters [14, 126, 131, 132]

us
Catalyst TOF
Entry Substrate Silane (eq.) Conditions Products (yield, %) TON Ref.
(mol %) (h–1)

an
1 MeCO2Me 47c (3) PhSiH3 (1.2) C6D6, RT, 0.25 EtOMe (85%)a 28 112 [131]

PhSi(OEt)3 (21%),a PhSi(OEt)2(OMe) (35%)a,

M
2 MeCO2Me 121 (1) PhSiH3 (1) C6D6, RT, 24 h 100 4.1 [14]
PhSi(OEt)(OMe)2 (17%),a PhSi(OMe)3 (26%)a

3 47a (3) PhSiH3 (1.2) C6D6, RT, 1.5 h Et2O (100%)a 33 22 [12]

ed
4 47c (3) PhSiH3 (1.2) C6D6, RT, 0.25 h Et2O (81%),a PhSiH(OEt)2 (19%),a 33 132 [131]
5 47c (3) Ph2SiH2 (1.2) C6D6, RT, 0.33 h Ph2HSiOCH(Me)OEt (95%),a,b Ph2SiH(OEt) (5%)a 33 100 [131]
MeCO2Et a,c a
6 47c (3.4) PhMe2SiH (1.2) C6D6, RT, 0.5 h PhMe2SiOCH(Me)OEt (89%), PhMe2SiOEt (11%) 29.5 59 [131]
pt
a a
7 121 (1) PhSiH3 (1) C6D6, RT, 5.5 h PhSi(OEt)3 (90%), PhSiH(OEt)2 (10%) 100 18.2 [14]
a
8 122 (1) PhSiH3 (1) C6D6, RT, 7 h PhSi(OEt)3 (>99%) 100 14.3 [126]
ce

9 MeCO2Pr-i 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h EtOPr-i (95%)a 31.6 63.3 [131]

PhSi(OEt)3 (37%),a PhHSi(OEt)2 (18%)a,

Ac

10 MeCO2Pr-i 121 (1) PhSiH3 (1) C6D6, 80 °C, 72 h 100 1.4 [14]
PhSi(OPr-i)3 (18%),a PhHSi(OPr-i)2 (27%)a

PhSi(OEt)3 (25%),a PhHSi(OBu-t)2 (30%)a,

11 MeCO2Bu-t 121 (1) PhSiH3 (1) C6D6, 80 °C, 240 h 85 0.35 [14]
PhHSi(OEt)(OBu-t) (30%)a

12 MeCO2Ph 121 (1) PhSiH3 (1) C6D6, RT, 240 h PhSi(OEt)3 (34%),a PhSi(OPh)3 (34%),a 95 0.4 [14]
a

114

Page 114 of 152

 t
ip
Edited June 30

cr
PhSi(OEt)2(OPh) (27%)a

PhHSi(OCH(Me)OTol-p)2 (49%),a EtOTol-p (5%),a

us
13 MeCO2Tol-p 47c (3) PhSiH3 (1.2) C6D6, RT, 0.25 h 33 132 [131]
PhHSi(OTol-p)2 and PhHSi(OEt)2 (46%)a

PhHSi(OTol-p)2 and PhHSi(OEt)2 (76%)a

an
14 MeCO2Tol-p 47c (3) PhSiH3 (1.2) C6D6, RT, 12 h 33 132 [131]
PhHSi(OCH(Me)OTol-p)2 (8%),a EtOTol-p (12%),a

15 PentCO2Et 47c (2) PhSiH3 (1.2) C6D6, RT, 0.5 h HexOEt (96%a, 81%d) 48 96 [131]

M
16 Br(CH2)3CO2Et 47c (3) PhSiH3 (1.2) C6D6, RT, 0.6 h Br(CH2)4OEt (92%a, 72%d) 30 50 [131]

17 i-PrCO2Et 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h i-PrCH2OEt (69%a, 61%d) 23 46 [131]

18 CyCO2Et 47c (3)

ed
PhSiH3 (1.2) C6D6, RT, 0.4 h CyCH2OEt (81%a, 70%d)

PhHSi(OCH(t-Bu)OMe)2 (40%),a
27 67 [131]
pt
19 t-BuCO2Me 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h t-BuCH2OMe (10%),a PhHSi(OMe)2 and 33 66 [131]
a
PhHSi(OCH2Bu-t)2 (46%)
ce

PhHSi(OCH(t-Bu)OMe)2 (16%),a
20 t-BuCO2Me 47c (3) PhSiH3 (1.2) C6D6, RT, 12 h t-BuCH2OMe (34%),a PhHSi(OMe)2 and 33 66 [131]
Ac

a
PhHSi(OCH2Bu-t)2 (50%)

21 47c (3) PhSiH3 (1.2) C6D6, RT, 0.4 h BnCH2OMe (92%a, 83%d) 30 76 [131]
BnCO2Me d
22 47c (2) Ph2SiH2 (1.1) C6D6, RT, 0.5 h Ph2HSiOCH(Bn)OMe (94% ) 47 94 [131]

23 (CH2CO2Et)2 47c (1.5) PhSiH3 (2.1) C6D6, RT, 0.33 h EtO(CH2)4OEt (83%a, 68%d) 110 330 [131]

115

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 t
ip
Edited June 30

cr
O O
O
24 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h (35%) d,e 11.6 23 [131]

us
O O O O
25 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h (40%) d,e 70 8.8 [131]

an
O O O O
26 47c (3) PhSiH3 (1.2) C6D6, RT, 0.5 h (65%) d,e 21.6 43 [131]

M
27 FpCO2Me 47a (2.1) PhMe2SiH (1) C6D6, RT, 3 h PhMe2SiOMe (100%)a, (η4-C5H6)Fe(CO)3 (100%)a,f 47.5 16 [132]

a1
28 FpCO2Me 47c (3.3)

H NMR product yield using internal standard

ed
PhSiH3 (1.1) C6D6, RT, 0.4 h
(η4-C5H6)Fe(CO)3 (92%)a, PhH2SiOMe (70%)a,
PhHSi(OMe)2 (30%)a
27 69 [132]
pt
b
81% isolated yield of Ph2SiH(OCH(Me)OEt) obtained using 2.1% of 47c under the same reaction conditions
c
ce

87% isolated yield of PhMe2SiOCH(Me)OEt obtained using 2.1% of 47c under the same reaction conditions
d
Isolated yield
e
Ring opening polymerization products were also observed
Ac

f
The product can be isolated in 90-92% yield

116

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Edited June 30

While the use of secondary and tertiary silanes leads to silylacetal products (entries 5, 6,
22), more reactive PhSiH3 promotes selectively the reductive cleavage of C–OSi bond within
the intermediate acetals to give in fine the corresponding ethers in good yield (entries 1, 4, 9,
15-18, 21, 23) with TOF up to 330 h–1 (entry 23) [131]. The selectivity of the reductive
cleavage of the C–OSi vs.C–OR bonds drops considerably for the acetals bearing aromatic
(entries 13, 14) or bulky aliphatic substituents (entries 19, 20). Though complexes 121 and

t
ip
122 are ca. 50 times more active than 47c in ketone hydrosilylation, a significantly lower
activity is observed in the hydrosilylation of esters (7, 8, 10-12) [14, 126]. Curiously, the

cr
latter catalytic system promotes only the reductive cleavage of C–OR bonds in the
intermediate acetals to afford almost statistical mixtures of alkoxysilanes.

us
Surprisingly, the catalytic hydrosilylation of FpCO2Me by complexes 47a and 47c
provides traces only of the expected acetal FpCH(OMe)(OSiR3), or of its reductive cleavage
product FpEt [132]. The formation of alkoxysilanes and the organometallic product (η4-

an
C5H6)Fe(CO)3 was observed instead (Table 6, entries 27, 28) as a result of concerted exo-
selective nucleophilic attack of the hydride on the Cp ligand, cleavage of C–OMe bond, and
CO de-insertion (Scheme 99).
M
H(D)
d

H
te

Fe OMe
R 3SiH(D)
Fe + R3SiOMe
47a or 47c CO
OC OC
OC OC
p

O
92-93%
ce

R 3SiH(D)
+ CO
CO R 3Si CO CO
Ac

CO Mn CO
H R 3Si Mn
R 3 Si Mn CO
CO L CO
L SiR 3 L
123 Fe OMe 123
OC
OC O

Scheme 99. Mn-catalyzed hydrosilylation of FpCO2Me [132]

Under photochemical activation CpMn(CO)3 promotes the catalytic hydrosilylation of

diethylformamide with PhMe2SiH (5% of catalyst, UV, C6D6, RT, 12-18 h) to give

117
Page 117 of 152
Edited June 30

PhMe2SiOCH2NEt2 in 95% yield. [133]. Subsequent treatment of the latter with an additional
equivalent of PhMe2SiH at high temperature in the presence of CpMn(CO)3 (5% of catalyst,
120 °C, 5 h) leads to quantitative formation of the corresponding disiloxane, (PhMe2Si)2O,
and Et2NMe. This reaction sequence can be also performed stepwise without the isolation of
the silyl ethers solely with the use of CpMn(CO)3 as catalysts (5% of catalyst, UV, RT, 12-18
h then heating at 120° for 24 h) to afford (PhMe2Si)2O in 80%, and 85% yields starting from

t
ip
dimethyl- and diethylformamide, respectively.
Sortais, Darcel and coll. reported the selective hydrosilylation of aliphatic carboxylic

cr
acids into disilylacetals promoted by Mn2(CO)10 (Scheme 100) [11]. The reaction is sensitive
to steric factors as aromatic carboxylic acids react sluggishly providing only 30-40%

us
conversion, and 2-phenylpropanoic acid is completely unreactive. The choice of tertiary
silanes (Et3SiH, PhMe2SiH, Ph2MeSiH) is crucial for the reaction chemoselectivity, more
active secondary silanes (Ph2SiH2, Et2SiH2) or tetramethyldisiloxane promoting the reductive

an
acetal cleavage to form silylethers. The process tolerates a variety of important functional
groups including unprotected amine, halogens, and heterocyclic moieties. The presence of
internal non-conjugated C=C double bond is well tolerated, whereas terminal alkene moiety
M
are partially hydrosilylated under reaction conditions. Though conjugated double bond and
hydroxyl group do not inhibit the reaction, contrary to nitro- and CF3 groups, concomitant
d

conjugated reduction and silylation, respectively, are observed.

te

R Ph o-Tol m-Tol p-Tol p-An

OSiEt3 83% 60% 87% 90% 93%
p

5% Mn 2(CO) 10, 3.3-5 eq Et3 SiH

R COOH R
UV, toluene or Et2 O, RT, 3-24 h R H Bn 1-Naph 2-thienyl
OSiEt3
ce

95% 96% 77% 70%

Other examples: OSiEt3

Ac

R R OSiEt3 OSiEt3
OSiEt 3
Et3 SiO OSiEt 3
N
H
R F Cl Br NH2 OSiEt 3 R H n-C12 H25 n-C15H 31
87% 82% 86% 85% 82% 97% 92% 98% 88%

OSiEt 3 Et3 SiO OSiEt3 OSiEt3 OSiEt 3

OSiEt 3 Et3 SiO OSiEt 3 OSiEt3 + Et3Si OSiEt 3

7 11 4 6
Oct
98% 97% 60% 32%

118
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Edited June 30

Scheme 100. Mn-catalyzed hydrosilylation of carboxylic acids to disilylacetals [11]

7.3. Mn-catalyzed electrochemical CO2 reduction

The development of manganese organometallic complexes for use in catalytic
electrochemical CO2 reduction was boosted by a seminal publication by Chardon-Noblat,
Deronzier and coll. in 2011 (Table 7) [15]. They reported that the Mn(I) complexes 127a-b,

t
ip
easily accessible from (CO)5MnBr and bipyridine derivatives, are prone to catalyze the
electrochemical reduction of CO2 into CO in the presence of water as a weak Brönsted acid,

cr
with a negligible electrochemical proton reduction. Very importantly, in these cases the
reduction process proceeds with overpotentials (entries 1-2) being ca. 0.35-0.4 V lower than

us
those of benchmark rhenium analogues, namely fac-(CO)3(bipy)ReBr, keeping a similar level
of selectivity, robustness, and faradaic efficiency.
Shortly after the above-mentioned publication, Kubiak and coll. found that the catalytic

an
activity of such complexes can be further enhanced both by introducing tert-butyl substituents
into the bipy ligand, and by using more apropriate weak acids (MeOH or TFE), albeit at
M
slightly higher overpotentials (entries 3-5) [16]. Finally, the same group reported that
complexes 127d and [128]+ bearing a mesityl group in ortho-position relative to the nitrogen
atoms of the bipy scaffold are largely outperforming all Mn-based catalytic systems reported
d

earlier, providing TOF up to 5000 s–1 in the presence of TFE (entry 8) [18]. Noticeably, the
te

presence of the bulky ligand prevents in that case the dimerization of the complex, a reaction
which is regarded as an undesirable de-activation pathway (vide infra).
p

Very recently, Nervi, Gobetto and coll. found that Mn-catalyzed CO2 reduction can be
ce

performed even in the absence of an external Brönsted acid, provided the bipy ligand contains
proximal hydroxyl groups, as found in complex 129 [19]. However, in that case, a decrease of
both the catalytic activity and chemoselectivity is observed, as revealed by the presence of
Ac

significant amounts of formic acid (entry 10).

The bipy moiety currently seems to be the most suitable ligand platform for the design
of efficient Mn catalysts. Besides, similar complexes based on NHC-pyridine (130-131) [17,
136] or diimine (132) [134, 135] were much less suitable (Table 7). Only the NHC-pyridine
complex 130b leads to selective CO production, yet with a moderate faradaic yield (entry 12),
whereas the other NHC-pyridine complexes exhibit lower efficiency in both CO2, and proton
reduction processes. Complexes 132a-c bearing diimine ligands are still capable of reducing
CO2 albeit being much less active, and this can be rationalized in terms of a lower

119
Page 119 of 152
 Edited June 30

nucleophilicity of the anionic manganese intermediates relative to their bipy analogues [134,
135].
Very recently, Nielsen and coll. predicted on the basis of DFT calculations that a
complex such as 133 bearing a bipyrimidine ligand should be capable of electrochemically
reducing CO2 like the bipy complex 127a at ca. 0.5 V lower overpotentials due to greater
electron affinity of this ligand [138].

t
ip
Table 7. Mn-catalyzed electrochemical reduction of CO2 [15-19, 134-136]

cr
R Mes Mes HO

us
Br Br NCMe
N N N Ph
CO CO CO
Mn Mn Mn OH
N Br

an
N CO N CO N CO CO
CO CO CO Mn

R Mes Mes TfO N CO

CO
R=H 127a
M
R = Me 127b 127d [128]+ 129
R = t-Bu 127c

R R
d
R'
N N
Br X Br Br
R N N N
te

N CO N CO CO CO
Mn Mn Mn Mn
N CO N CO R N CO N N CO
CO CO CO CO
p

R'
ce

R = Me, X = Br 130a R = Me, X = Br 131a R = H, R' = i-Pr 132a 133

R = Et, X = Br 130b R = Et, X = Br 131b R = Me, R' = Mes 132b
R = Et, X = CN 130c R = Et, X = CN 131c R = Me, R' = Dipp 132c
Ac

R = Et, X = SCN 130d

Ea
Bronsted TOFCO ρCOb Other products
Entry Cat. (mM) (V vs Ref.
acid (M) (s–1) (%) (ρ, %)
Fc)

0.14,c
1 127a (1) H2O (2.7) –1.74 85 H2 (15) [15]
0.89d

2 127b (1) H2O (2.7) 2.33d –1.74 100 none [15]

120
Page 120 of 152
 Edited June 30

3 127c (1) H2O (3.1) 120c - - - [16]

MeOH
4 127c (1) 130c - - - [16]
(5.8)

5 127c (1) TFE (1.4) 340,c 267d,e –2.2 100±15 none [16]

t
6 127d (1) H2O (3.5) 700c - - - [18]

ip
MeOH
7 127d (1) 2000c - - - [18]
(3.2)

cr
8 127d (1) TFE (1.4) 5000c - - - [18]

us
[128]+
9 TFE (0.3) 480d –2.2 98±6 none [18]
(0.5)

an
H2 (1%)
10 129 (1) none 1.4 –2.18 70 HCOOH [19]
(22%)
M
11 130a (1) H2O (2.7) 0.08c –1.84 33 H2 [17]

12 130b (1) H2O (2.7) 0.86c –1.91 67 none [136]

d

13 130c (1) H2O (2.7) 0.38 –2.34 20.5 H2 [136]

te

14 130d (1) H2O (2.7) 0.5 –2.01 27 H2 (53%) [136]

p

15 131a (1) H2O (2.7) 0.07c - - H2 (53%) [17]

ce

16 131b (1) H2O (2.7) 0.28 –2.23 30 H2 (53%) [136]

a
Working potential on bulk CPE (carbon rod working electrode, MeCN, 0.1M Bu4NPF6, RT, 4-
24 h)
Ac

b
Faradaic yield upon bulk CPE
c
Calculated from catalytic current values obtained by CV (GC working electrode, MeCN, 0.1M
Bu4NPF6, RT) according to equation given in ref. [16]
d
Calculated from CPE data using Savéant’s method [137]
e
CPE performed using 5 mM concentration of 127c in the presence of 0.8 M TFE

The mechanism of the Mn-catalyzed CO2 reduction (Scheme 101) was thoroughly
studied both experimentally using spectroelectrochemistry [16, 18], pulse ESR [139] and
TRIR [140] experiments, and theoretically through DFT calculations [138, 141, 142]. It was
121
Page 121 of 152
Edited June 30

proposed that the initial one-electron reduction of complex 127 leads to the formation of the
corresponding 19ē radical anion that undergoes a bromide elimination to afford the neutral
19ē radical 134• (path a-b) [140]. The latter species can be further reduced into anionic [134]–
(path c), or directly coupled to form the dimeric product 136 (path i), which can in turn be
slowly transformed into [134]– by a two-electron reduction at ca. 0.3-0.4 V more negative
potential (path l). While for pre-catalysts 127a-c the dimerization process is strongly preferred

t
ip
[15,16], the radical 134• formed from complex 127d is stable towards dimerization, evolving
exclusively toward [134]– via the reduction pathway, thereby generating a higher

cr
concentration of catalytically active species [18]. This correlates well with the much higher
catalytic activity of 127d relative to the rest of the series (Table 7, entry 6 vs. 1-3). The

us
catalytic cycle of CO2 reduction (paths d-h) includes the formation of the anionic complex
[135]–, followed by its systematic protonation by the weak Brönsted acid to form the neutral
carboxylate intermediate 137, thus rendering the process thermodynamically favorable. The

an
latter undergoes again a one-electron reduction with concomitant protonation and elimination
of a water molecule to form the cationic complex [138]+, releasing a CO molecule upon
M
subsequent reduction and regeneration of [134]–. Very importantly, the bipy ligand is acting
not only as an electron donor favoring CO2 binding at the metal center, but also as a non-
innocent redox center. Indeed, most of the reduction processes shown in Scheme 101 are
d

initially bipy-ligand centered [141]. According to DFT calculations, the dehydroxylation step
te

(f) is rate determining [138, 141, 142]. The activation barrier for the protonation of [134]– into
the hydride complex 139 (path n), capable to produce hydrogen upon reduction/protonation
p

sequence, is more than 10 kcal/mol higher than for CO2 coordination [138, 141, 142], fully
ce

consistent with the excellent experimentally observed chemoselectivity.

Ac

122
Page 122 of 152
Edited June 30

Br Br CO
N CO N CO N .
+e Br
Mn . Mn Mn CO
(a) (b)
N CO N CO N
CO CO CO
127 [127 ]
. 134
.
+e
(c) (i)

t
H CO
N N

ip
CO + H+ CO
Mn Mn CO
(n) OC N
N CO N Mn
CO CO

cr
+2e OC N
139 [134 ]
(h) (l) N CO
+e
(d) CO2 Mn

us
N CO
CO
CO CO CO
136
N . CO N CO
Mn Mn

an
N CO N COO (k) CO2 + H+
CO CO
138
. [ 135 ] CO
N CO
H+
M
(e) Mn
+ e (g)
N COOH
CO
CO CO
N CO N CO [137 ]+
+ e, + H + +e
Mn
d
Mn
(f) (m)
N CO N COOH
CO CO
te

H 2O
[138 ]+ 137
p

Scheme 101. Mechanism of the electrochemical CO2 reduction catalyzed with Mn-bipy
ce

complexes 127-129 [16, 18, 138-142].

The dimeric complexes 136 obtained from 127b, can operate via an alternative CO2
Ac

reduction pathway (k, m, f-h) [139], which includes the formation of a cationic carboxylate
complex [137]+ upon concerted reaction of 136 with CO2 and the Brönsted acid, followed by
its one-electron reduction into the common intermediate 137 that evolves further as described
above.
The observation of an electrochemical CO2 reduction taking place in aqueous media
using complex 127a supported in a Nafion membrane as a working electrode was recently
reported by Cowan and coll. [21]. A 1:2 CO/H2 syngas mixture was selectively produced with
ca. 75% faradaic efficiency upon bulk electrolysis at –1.4-1.5 V vs. Ag/AgCl electrode under
neutral pH conditions. The addition of multi-walled carbon nanotubes to the electrode
123
Page 123 of 152
Edited June 30

material composition leads to a dramatic enhancement of the effective current density keeping
the same chemoselectivity for syngas production and robustness of the heterogeneous
catalytic system.
While formic acid was formed as a by-product along with CO in the electrochemical
CO2 reduction using complex 129 (TON of 6, and 19 for HCOOH, and CO, respectively)
[19], it could be produced much more selectively upon photoreduction of CO2 using complex

t
ip
127a in the presence of a Ru-based photosensitizer and 1-benzyl-1,4-dihydronicotinamide as
a sacrificial reductant [20]. Using a 4:1 mixture of MeCN or DMF with triethanolamine,

cr
HCOOH was produced with TON of 78 and 149, respectively, in ca. 5% quantum yield, along
with CO (TON of 40 and 12, respectively) and hydrogen (TON of 17 and 14, respectively).

us
Though the exact mechanism of HCOOH formation remains unclear, it could originate from
the protolysis of the Mn–COOH bond in the one-electron reduced complex [137]– to give the
hydride complex actually 139 responsible for the hydrogen production process (Scheme 101,
path f).

an
M
8. Mn-catalyzed electrochemical hydrogen production
Electrocatalytic hydrogen production mediated by manganese organometallic
compounds was first reported by Ustynyuk and coll. using vinylidene and allenylidene
d

complexes 140 and 141 (Table 8, entries 1-2) [143]. Both complexes catalyze the reduction of
te

the strong acid HBF4 in CH2Cl2 or MeCN media with moderate efficiency but at relatively
low working potential. These catalytic systems represent the first examples of electrochemical
p

proton reduction based on the formation and activation of a C–H bond, rather than the more
ce

common M–H bond activation (Scheme 102). Indeed, the catalytic cycle starts with the
protonation of the metallacumulene complex to form the cationic 18ē carbyne [148]+, which
then undergoes reduction to the corresponding 19ē radical species 148•, eliminating hydrogen
Ac

as a result of a metal-assisted homolytic C–H bond cleavage [143].

Table 8. Mn-catalyzed electrochemical proton reduction [22-25, 143-144]

124
Page 124 of 152
Edited June 30

OH2
Mn S S CO
. Ph Mn .
Ph 3P OC . Ph Ni Mn
OC OC S S CO
H CO
Ph
140 141
Br
[142 ]+

t
RS Pi-Pr3
PCy 3 PCy 3

ip
OC S S CO CO CO
OC S CO OC S CO
OC Mn Re CO Re Mn Re Mn

cr
H OC S CO OC S CO
OC CO PPh3 Bu CO N Bu CO

R = Me 143a

us
R = Bu 143b 144a 144b

Ph 2 Et Ph

an
S CO
P OC Ph S CO
X S
N Ni Mn CO OC Mn Mn CO
p-Tol P S S S
CO OC CO S
Ph2 Et S OC CO
Mn Mn
M
Ph
OC S CO
X = Cl 145a CO CO (bipy) 3 Mn
X = Br 145b 146 [147]
d

Ea (V vs.
Entry Cat. Brönsted acid Solvent ∆Eb (V) ρ(H2)c Ref.
Fc)
te

1 140 HBF4•OEt2 MeCN –1.60 1.53 - [143]

p

2 141 HBF4•OEt2 MeCN –0.84 0.77 - [143]

ce

3 [142]+ CF3COOH DMF –1.82 0.86 94% [22]

4 143a CH3COOH MeCN –2.07 0.78 80%d [144]

Ac

5 143b CH3COOH MeCN –2.11 0.82 - [144]

6 144a CH3COOH MeCN –1.96 0.67 90%d [144]

7 144b CH3COOH MeCN –2.07 0.78 - [144]

8 145a CH3COOH MeCN –1.80 0.51 90% [23]

9 145b CH3COOH MeCN –1.79 0.50 90% [23]

10 146 CF3COOH MeCN –1.50 0.79 75% [24]

11 [147]– CH3COOH DMF –2.10 0.73 80% [25]

125
Page 125 of 152
Edited June 30

a
Catalytic peak potential of H2 production obtained from CV data (GC working electrode,
0.1M n-Bu4NPF6, RT)
b
Overpotential of the electrochemical H2 production calculated according to ref. [145]
c
Faradaic yield upon bulk CPE
d
CPE was carried out at –2.2 V vs. Fc

t
ip
Mn .

cr
R'
L
1/2 H 2 OC H+
R

us
140-141

an
Mn
. R' R'
. Mn .
L H L H
OC OC
M
. R R
148 [ 148 ]+

+e
d

Scheme 102. Proposed catalytic cycle for electrochemical reduction of HBF4 with manganese
te

metallacumulene complexes [143]

p

Numerous examples of binuclear manganese-containing hydrogenase active site models

ce

bearing thiolate ligand bridges were further prepared, including MnNi [22, 23], MnRe [143],
and MnMn [24, 25] cores (Table 8). All these complexes catalyzes efficiently the reduction of
Ac

acetic or trifluoroacetic acid in polar organic solvents with, typically, 0.5-0.85 V

overpotentials, and good to excellent faradaic efficiencies. Importantly, the anionic complex
[147]– is capable to keep an high activity even in the presence of a huge amount of acid
affording the estimated TOF of ca. 44600 s–1 at RT [24], which is comparable with the best
iron-based catalysts (TOF of 58000 s–1 [146]) and nickel ones (TOF of 106000 s–1 [147])
known so far, both displaying similar overpotential values.
On the basis of DFT calculations and electrokinetic simulations, Artero and coll.
showed that the catalytic hydrogen production for the MnNi complex [142]+ proceeds via an
ECCE mechanism (Scheme 103) with a heterolytic metal-hydride bond activation, similar to

126
Page 126 of 152
Edited June 30

the one found in natural FeNi hydrogenases [22]. The catalytic cycle includes two consecutive
one-electron reduction processes giving the anionic intermediate [149]–, which undergoes a
protonation to afford the neutral complex 150 exhibiting a bridging hydride ligand. Further
protonation of the latter leads to the formation of the manganese dihydrogen complex [151]+,
from which the dihydrogen dissociation occurs, with concomitant regeneration of the neutral
complex 149.

t
ip
cr
OH 2
S S CO
Ni Mn

us
S S CO
CO

[142] +

an
+e
M H 2O

CO
S S
Ni Mn CO
H2 S S
CO
d
+e
te

149

H H CO
S S S S
p

CO
Ni Mn Ni Mn CO
S S CO S S
ce

CO CO

[151]+ [149]
Ac

H
H + S S CO H+
Ni Mn
S S CO
CO

150

Scheme 103. Proposed catalytic cycle for the electrochemical hydrogen production catalyzed
by the MnNi complex [142]+ [22]

127
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Edited June 30

Proton reduction to hydrogen is also catalyzed by the bimetallic thiolate-bridged

manganese carbonyl complexes 146 and [147]– [23, 24]. In contrast to the previous case, the
thiolate moieties are directly involved in the hydrogen generation process (Schemes 104 and
105, respectively). The reaction mechanism proposed for the neutral binuclear complex 146 is
supported by DFT calculations. It includes the initial two-electron reduction of 140 leading to
the dianionic species [152]2– (Scheme 104) [24]. The latter undergoes a stepwise protonation

t
ip
of the thiolate and of the metal center to give 154, followed by an intramolecular proton
transfer from a coordinated thiol moiety to the hydride ligand to form the dihydrogen complex

cr
155. Release of dihydrogen leads to the formation of the 16ē complex 156, which dimerizes to
regenerate complex 146.

us
OC
S

Mn
an
S
S

Mn
CO
+2 e
M
OC S CO
CO CO
S 146 S
CO 2 CO
S Mn S Mn
d

CO CO
CO CO
te

156 [ 152 ]2
H2
p

H+
ce

S
CO
S HS Mn
S CO
Mn CO
CO
Ac

H S
CO CO
H CO HS [153 ]
Mn
155
H CO H+
CO
154

Scheme 104. Proposed catalytic cycle for the electrochemical hydrogen production catalyzed
by dimanganese complex 146 [24]

For the anionic complex [147]– the catalysis proceeds as a CECE sequence, including an
initial protonation of the thiolate moiety, followed by a reduction of the resulting complex 157
128
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Edited June 30

with concomitant S-to-Mn proton transfer to form the anionic complex [158]– exhibiting a
terminal hydride ligand. Its further protonation leads to the dihydrogen complex 159, from
which a one-electron reduction induces dihydrogen elimination, and regeneration of [147]–.
Ph
OC Ph S CO
H2 S H+
OC Mn Mn CO

t
S

ip
+e OC CO
Ph
Ph [147] Ph

cr
OC Ph S CO Ph S CO
OC
S S
OC Mn Mn CO Mn Mn CO
H S OC HS

us
OC CO CO CO
H
Ph Ph
Ph
159 +e 157
OC Ph S CO

an
S
OC Mn Mn CO
H+ S
OC H CO
Ph
M
[ 158 ]

Scheme 105. Proposed catalytic cycle for the electrochemical hydrogen production catalyzed
d

by the dimanganese complex [147]– [23]

te

9. Mn-catalyzed dehydrogenative coupling processes via heteroatom-H bond activation

p

Various manganese carbonyl complexes promote the dehydrogenative silane alcoholysis

ce

under neutral conditions to produce alkoxysilanes, hydrogen being the only byproduct of the
reaction [148-152]. Hilal and coll. originally reported that the reaction between tertiary silanes
(EtO)3SiH or Et3SiH, and primary alcohols like MeOH or EtOH in the presence of 1.25% of
Ac

Mn2(CO)10 and PPh3 produces the corresponding alkoxysilane with 50% silane conversion
after 0.25-2.5 h at 30 °C [148]. The reaction is faster in non-polar solvents such as hexane or
toluene. Yet, even under these conditions, secondary and tertiary alcohols are almost
unreactive. Later, Barton and Kelly showed that irradiation with visible light is mandatory to
activate Mn2(CO)10 for the alcoholysis of more reactive PhSiH3 with t-BuCH2OH at RT,
affording up to 3000 TON for PhSiH2OCH2Bu-t under neat conditions [149]. The efficiency
and substrate scope of this process was largely improved by Butler and coll. using manganese
carbonyl bromide complexes (Scheme 106) [150].

129
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Edited June 30

0.084% [(CO) 4 MnBr]2 R Me Et i-Bu t-Bu All p-An

ROH + Me2PhSiH Me 2PhSiOR
C 6D 6 or CH2Cl2, RT, 0.15-2.5 h 93% 92% 82% 82% 88% 36%

Other examples:

OSiMe2Ph OSiMe2 Ph
Br OSiMe 2Ph PhMe 2SiO OSiMe 2Ph

t
88% 92% O 89% 78%

ip
OSiMe 2Ph
MeO EtOSiEt3

cr
64% 100%

us
Scheme 106. Mn-catalyzed dehydrogenative alcoholysis of tertiary silanes [150]

The mononuclear complex (CO)5MnBr is less active than the dimeric [(CO)4MnBr]2,

an
which can reach TOF of ca. 11200 h–1 in the reaction between i-BuOH and Me2PhSiH [150].
Different types of alcohols and the less reactive tertiary silanes can be engaged in this process,
producing alkoxysilanes at RT in quantitative yields, as measured by NMR. However, p-
M
methoxyphenol reacts very sluggishly even after prolonged reaction time. The reaction of
phenol with Et3SiH catalyzed by [mer-(CO)3(CH2Cl2)Mn(P(OCH2)3CMe)2]BARF was
d

reported by Kubas and coll. to give Et3SiOPh in 50% yield (4.15% catalyst, CD2Cl2, –80 °C
te

to RT) [151].
Bulky tertiary silanes derived from optically active ethyl lactate and i-Pr2SiH2 can be
p

used in Mn-catalyzed dehydrogenative alcoholysis to afford the unsymmetrical dialkoxysilane

products in moderate to good yields (Scheme 107) [152]. Though a number of noble metal
ce

complexes are known to catalyze dehydrogenative silane alcoholysis with higher TOF values
than offered by manganese, a drawback of such systems is the occurrence of a competitive
Ac

hydrosilylation of the functional groups mentioned above. Very importantly, both Mn-based
protocols show an excellent tolerance to the presence of functional groups such as terminal
alkene or alkyne moieties, aliphatic or aromatic bromide substituents, and even carbonyl
groups like esters and ketones. As illustrative example, the [(CO)4MnBr]2-catalyzed
alcoholysis of Me2PhSiH with i-BuOH in the presence of acetone proceeds to completion,
without any traces of ketone hydrosilylation products [150].

130
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Edited June 30

R
R i-Pr 2
4% (CO) 5 MnBr Si
+ O CO2Et
H(i-Pr) 2 Si CO2 Et CH 2Cl2, RT, 2 h O
OH
R H Me All Ph
68% 67% 62% 51%
Other examples:

t
i-Pr 2 i-Pr 2 i-Pr 2

ip
Si Si Br Si
O O CO2 Et O O CO2Et O O CO2 Et

70% 56% 68%

cr
Br Br Br
i-Pr 2 i-Pr 2 i-Pr 2

us
Si Si Si
n O O CO2Et O O CO2Et O O CO2Et

n = 1 75% Br 33% 70%

an
n = 2 65%

Scheme 107. Mn-catalyzed dehydrogenative alcoholysis of bulky tertiary alkoxysilanes [152]

M
The proposed reaction mechanism (Scheme 108) includes the formation of
coordinatively unsaturated complex 160, which, however, must be present in the reaction
d

mixture in extremely low concentration since IR monitoring of the catalytic reaction shows
te

[(CO)4MnBr]2 only. This complex undergoes a coordination of silane followed by the

formation of the alkoxysilane product and of the dihydrogen complex 162 as a result of a
p

stepwise or concerted nucleophilic attack of the oxygen atom at the coordinated silyl group,
and proton transfer from oxygen atom to hydride ligand. However, the formation of
ce

silylbromide by reductive elimination from 161 followed by its reaction with alcohols cannot
be excluded.
Ac

131
Page 131 of 152
Edited June 30

[(CO) 4MnBr] 2 CO (CO) 5MnBr

CO
CO
Br Mn
CO R 3SiH
H2 CO
160

t
ip
CO CO
Br CO Br CO

cr
Mn Mn
H R 3Si
CO CO
H CO H CO

us
162 161

an
R'OSiR3 R'OH

Scheme 108. Proposed mechanism for the Mn-catalyzed dehydrogenative silane alcoholysis
M
[150]

Recently, Fan and coll. reported a selective dehydrogenative coupling of thiols into
d

disulfides using CpMn(CO)3 [153] or (CO)5MnBr [154] under UV irradiation (Scheme 109).
te

Curiously, in the latter case, the reaction proceeds only in the presence of oxygen and includes
free radical intermediates. Their implication was demonstrated by parallel experiments
p

showing that the addition of radical scavengers like TEMPO and pyrogallol decreases
ce

significantly the product yields [154]. A variety of important functional groups including
hydroxyl, amine, ester, and silane are tolerated in this process. The presence of a free
carboxylic acid group inhibit the coupling process when using (CO)5MnBr, but anionic
Ac

carboxylate moieties are tolerated if the reaction is carried out in water or water/t-BuOH
mixtures [154].

132
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Edited June 30

R Bu Oct n-C12H25 n-C16H 33 Bn

3% CpMn(CO) 3, UV, RT, 2.5 h (A)
RSH RSSR A 95% 94% 94% 95% -
or 5% (CO) 5MnBr, O2, UV, RT, 2 h (B ) B 90% 89% 89% - 81%

Other examples:

S CO2Et HO S
p-TolSSTol-p CySSCy EtO2C S S OH

t
ip
94% (A) 56% (B) 99% a (A), 20% a (B) 99% a (A), 89% a (B)

HO

cr
NH2 O
S H
S N
O2C N CO2
H

us
OH O
80% a ( A), 99% a ( B) S
S
O

an
(MeO) 3Si S H
S 3 Si(OMe) 3 O 2C N CO2
3
N
76% a (A), 45% a (B) H
O NH2
M
63% a (B)
NH2
S O EtO2C S CO2
S
S S CO2Et O 2C S
O
d

NH2
77% a (A), 59% a (B) 99% a (B) 40% a (B)
te

Scheme 109. Mn-catalyzed dehydrogenative coupling of thiols (a NMR product yield using
internal standard) [153, 154]
p
ce

A mechanism based on DFT calculations was proposed for the catalytic system based
on CpMn(CO)3 [155] (Scheme 110). It includes the photochemically induced displacement of
Ac

a CO ligand by the thiol to give 163, followed by an intramolecular proton transfer from the
thiol moiety to the Cp ring to give the η4-diene intermediate 164 allowing the uptake of a
second thiol molecule to produce 165. Subsequent concerted elimination of molecular
hydrogen concomitant with S–S bond formation leads to 166, from which displacement of the
disulfide product by an incoming thiol regenerates 163. The reaction mechanism in the case of
(CO)5MnBr-catalyzed thiol dehydrocoupling requiring the presence of oxygen remains
obscure.

133
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Edited June 30

Mn
OC CO
OC

RSH CO

t
ip
RSSR
Mn H
RSH OC S
OC

cr
R H
163
H

us
R
Mn S Mn
OC S OC S
OC OC
R R

an
H
166 164
H

H
M
Mn
H2 OC S RSH
OC S
R
R
d

165
te

Scheme 110. Proposed catalytic cycle for CpMn(CO)3-catalyzed dehydrogenative coupling of

p

thiols [153, 155]

ce

Dehydrogenative dimerization of secondary amine-boranes catalyzed by CpMn(CO)3

under photochemical activation produces cyclic aminoboranes in good yield (Scheme 111)
Ac

[156]. The use of primary amine-borane MeNH2•BH3 under the same reaction conditions
produced the corresponding aminoborane polymer.
H2 H2
B B
5% CpMn(CO)3
H 3B NR2 H R2N NR2 N N
C6 D6, UV for 1 h then 24-48 h at RT
B B
H2 H2

R = Me 93% 73%
R = Me 68%

Scheme 111. Mn-catalyzed dehydrogenative dimerization of amine-borane adducts [154]

134
Page 134 of 152
Edited June 30

10. Miscellaneous reactions

In 1993 Cutler and coll. reported the efficient H/D exchange between Me2EtSiH and
Me2PhSiD catalyzed with (CO)5MnCOTol-p in benzene at RT [157]. The reaction was
proposed to proceed via the formation of silyl-silane intermediate (CO)4(R3SiH/D)MnSiR3.
The Mn-catalyzed ring-opening oligomerization of 2-thietanone giving the macrocyclic
head-to-tail tetramer along with linear products was reported by Adams and coll. (Scheme

t
ip
112) [158]. The reaction can be catalyzed either by Mn2(CO)10 or Mn2(CO)9(MeCN) giving in
the latter case 13.5%, and 62% yield of tetramer, and oligomers, respectively. The manganese

cr
cationic complexes [(CO)4(L)Mn(MeCN)]BPh4 (L = CO, PPh3, PMe2Ph, PEt3) catalyze the
oligomerization of thiirane at RT to form a mixture of 12S4, 15S5, and 18S6 thiacrown ethers

us
as well as open chain oligomers [159].

an
O
O
S S
0.087% Mn2(CO) 10
+ (SCH2CH2CO)n
CH2Cl2, RT, 24 h
M
S S S 35%
O
O
O 19%

Scheme 112. Mn-catalyzed oligomerization of 2-thietanone [158]

d
te

Manganese complexes catalyze the selective formation of cyclic carbonates from

epoxides and CO2 under neat conditions (Table 9) [160, 161]. A variety of monosubstituted
p

epoxides could be efficiently transformed under these conditions, whereas disubstituted

ce

epoxides such as epoxycycloxexane provided traces only of the desired products. Though the
anionic complex Li[45] exhibited moderate activity with TOF of 100-175 h–1 for activated
substrates at increased CO2 pressure (entries 8, 21, 27, 33), the corresponding PPN salts were
Ac

generally ca. 5-10 times more active (TOF up to 850 h–1) [160]. The binuclear MnRu complex
168a is generally 50% more active than both Li[45] and 168b, showing a beneficial effect of
cooperative catalysis (vide infra).

Table 9. Mn-catalyzed synthesis of cyclic carbonates from epoxides and CO2 [160, 161]

135
Page 135 of 152
Edited June 30

R
R R
CO CO CO
R CO
CO CO R R
R' OC Mn OC Mn Ru Mn CO
O Cat OC
+ CO2 O O CO CO
R 100 °C Li CO PPN L Ph2P OC PPh2
R' O Li[45] L = CO PPN[45] R=H 168a

t
L = PPh3 PPN[167] R = Me 168b

ip
entry R R’ Cat. (%) Conditions TON TOF (h–1) Ref.

cr
1 Li[45] (0.1) 5 bar CO2, 6 h 60 10 [160]
2 Li[45] (0.011) 40 bar CO2, 40 h 440 11 [161]

us
3 PPN[45] (0.1) 5 bar CO2, 6 h 669 112 [160]
H Me
4 PPN[167] (0.1) 5 bar CO2, 6 h 624 104 [160]
5 168a (0.011) 40 bar CO2, 40 h 1490 37 [161]

an
6 168b (0.011) 40 bar CO2, 40 h 450 11 [161]

7 Li[45] (0.011) 40 bar CO2, 40 h 1795 45 [161]

M
8 PPN[45] (0.1) 5 bar CO2, 6 h 624 104 [160]
9 H Et PPN[167] (0.1) 5 bar CO2, 6 h 642 107 [160]
10 168a (0.011) 40 bar CO2, 40 h 2800 70 [161]
d

11 168b (0.011) 40 bar CO2, 40 h 1940 48 [161]

te

12 Li[45] (0.011) 40 bar CO2, 40 h 110 3 [161]

13 PPN[45] (0.1) 5 bar CO2, 6 h 628 105 [160]
p

14 H Bu PPN[167] (0.1) 5 bar CO2, 6 h 634 106 [160]

ce

15 168a (0.011) 40 bar CO2, 40 h 480 12 [161]

16 168b (0.011) 40 bar CO2, 40 h 120 3 [161]
Ac

17 PPN[45] (0.1) 5 bar CO2, 6 h 653 109 [160]

Me Me
18 PPN[167] (0.1) 5 bar CO2, 6 h 627 105 [160]

19 PPN[45] (0.1) 5 bar CO2, 6 h 772 129 [160]

H Ph
20 PPN[167] (0.1) 5 bar CO2, 6 h 783 131 [160]

21 Li[45] (0.011) 40 bar CO2, 40 h 7020 176 [161]

22 PPN[45] (0.1) 5 bar CO2, 1 h 876 876 [160]
H CH2F
23 PPN[167] (0.1) 5 bar CO2, 1 h 847 847 [160]
24 168a (0.011) 40 bar CO2, 40 h 8640 216 [161]

136
Page 136 of 152
Edited June 30

25 168b (0.011) 40 bar CO2, 40 h 7050 176 [161]

26 Li[45] (0.1) 5 bar CO2, 1 h 23 23 [160]

27 Li[45] (0.011) 40 bar CO2, 40 h 5400 135 [161]
28 PPN[45] (0.1) 5 bar CO2, 1 h 853 853 [160]
H CH2Cl
29 PPN[167] (0.1) 5 bar CO2, 1 h 809 809 [160]

t
30 168a (0.011) 40 bar CO2, 40 h 8000 200 [161]

ip
31 168b (0.011) 40 bar CO2, 40 h 5300 132 [161]

cr
32 Li[45] (0.1) 5 bar CO2, 1 h 19 19 [160]
33 Li[45] (0.011) 40 bar CO2, 40 h 4100 103 [161]

us
34 PPN[45] (0.1) 5 bar CO2, 1 h 846 846 [160]
H CH2Br
35 PPN[167] (0.1) 5 bar CO2, 1 h 808 808 [160]
36 168a (0.011) 40 bar CO2, 40 h 6450 161 [161]

an
37 168b (0.011) 40 bar CO2, 40 h 4200 105 [161]

The proposed reaction mechanism for the process catalyzed by anionic manganate
M
complexes starts with a nucleophilic addition to CO2, giving the carboxylate [169]– which
further reacts with the epoxide to give the intermediate [170]– bearing an alkoxide
d

functionality (Scheme 113). The latter undergoes an intramolecular SN2 nucleophilic

te

substitution to form the final carbonate product that is released with concomitant regeneration
of the starting anionic species. The observed difference in activity between the lithium and
PPN salts can be attributed to a stronger nucleophilicity of (CO)4(L)Mn– in the presence of the
p

non-coordinating PPN+ cation, thus facilitating the CO2 activation step.

ce

A different mechanism, based on DFT calculations, was proposed for the same reaction
catalyzed by the bimetallic Mn-Ru complexes 168 (Scheme 114). The cycle starts with the
Ac

coordination of the epoxide to the ruthenium and concomitant Mn–Ru bond cleavage. The
epoxide thus activated undergoes a ring opening induced by intramolecular nucleophilic
attack of the pendant manganate anion to give the complex 172, which undergoes a CO2
insertion across Ru–O bond. A subsequent binuclear reductive elimination produces the cyclic
carbonate product and regenerates 168 thus closing the cycle.

137
Page 137 of 152
Edited June 30

R CO
OC
Mn CO CO2
O O
OC
L
O
L = CO [42 ]
L = PPh3 [167 ]

t
CO CO

ip
OC CO OC CO
Mn O Mn O
OC C OC C

cr
L O
L
O O
[170] R [169]

us
O

an
Scheme 113. Proposed catalytic cycle for the formation of cyclic carbonates from epoxides
and CO2 catalyzed by anionic manganate species [160]
M
R
O
d

O O
Ru Mn(CO) 4
OC R
te

O
Ph2 P PPh2

168
p

R
O R
ce

O
O O
Ru Mn(CO) 4 Ru Mn(CO) 4
OC OC
Ac

Ph2 P PPh2 Ph2 P PPh2

173 171

O
Ru Mn(CO) 4
CO2 OC
Ph2 P PPh2

172

138
Page 138 of 152
Edited June 30

Scheme 114. Proposed catalytic cycle for the formation of cyclic carbonates from epoxides
and CO2 catalyzed by bimetallic MnRu complexes 162 [161]

The dimerization of isocyanates to carbodiimides with elimination of CO2 is catalyzed

by Cp’Mn(CO)3 (Scheme 115) [162]. Though the carbodiimides are isolated in relatively low
yields after crystallization, GC and NMR analysis shows that the product yields are actually

t
ip
30-40% higher. Even though the reaction is conducted at 140 °C only small amounts of
isocyanate dimerization and trimerization products is also detected.

cr
R
0.5-1% Cp'Mn(CO) 3
RNCO N . N
R Ph p-An p-ClC6 H4 Cy TMS

us
xylene, 140 °C, 48-72 h 43% 22% 34% 28% 12%
R
Scheme 115. Mn-catalyzed synthesis of carbodiimides from isocyanates [162]

an
The dimerization of p-TolNCO can be also catalyzed by 1.7% of [(CO)4MnH]3 or 10%
of Mn2(CO)10 to give the corresponding carbodiimide in 48%, and 62% yields, respectively
[163].
M
The proposed catalytic cycle is based on a nucleophilic attack of the nitrogen atom of
free isocyanate molecule at the carbon atom of the activated isocyanate ligand in complex
174, followed by a CO2 extrusion from the resulting intermediate 175, and substitution of the
d

carbodiimide ligand with another isocyanate molecule (Scheme 116).

p te
ce
Ac

139
Page 139 of 152
Edited June 30

Mn
OC CO
OC

RNCO CO

t
.

ip
N N O
R Mn .
OC N
RNCO

cr
OC
R
174

us
RNCO

R
O

an
N O
Mn . Mn N
N OC N
OC R
OC OC
R R
M
176 175
d
te

CO2
p

Scheme 116. Proposed catalytic cycle for the Mn-catalyzed formation of carbodiimides from
isocyanates [162]
ce

Mn-catalyzed reaction of enolizable aliphatic ketones with carbodiimides results in a

Ac

selective carbon-carbon bond cleavage producing amides in good to excellent yields

averaging 70%, along with poly-substituted quinoline as byproduct (Scheme 117) [163]. The
process can be efficiently catalyzed by Mn2(CO)10 (5%) at 150 °C. The use of the trinuclear
hydride complex [(CO)4MnH]3 as pre-catalyst allows a decrease of the reaction temperature
to 135 °C, probably due to a more facile pre-catalyst activation process (vide infra). Though
the reaction with p-TolN=C=NTol-p provides the highest yields of amides from aryl ethyl
ketones, substrates bearing other substituents such as Me, Hex, i-Pr and Bn undergo the same
transformation with 60-95% yields. In the case of non-symmetric aliphatic ketones such as
CyCOEt the selective cleavage of the C–C bond with primary alkyl substituent takes place

140
Page 140 of 152
Edited June 30

albeit in lower yield (50%). The synthetic scope of this method is quite broad providing
generally almost quantitative yields of amides from aromatic ketones, with a slight decrease
of the reaction efficiency in the case of aliphatic substrates. Interestingly, the same reaction
can be performed from isocyanates using in situ Mn2(CO)10-catalyzed generation of
carbodiimides. However, significantly lower product yields are obtained, even with an
increased catalytic charge [163].

t
ip
O

cr
O NHTol-p

1.7% [(CO) 4MnH]3 NHp-Tol

+

us
R
dioxane, 135 °C, 24 h
p-Tol
+ R p-TolHN N
N . N
R H Me OMe Cl Br CF3

an
Tol-p
3 eq 96% 96% 98% 96% 62% 96%

Other examples:
M
O O O

R NHp-Tol Ph NH R Ph NHR
d

R Pent Cy R H OMe Cl Br CF3 R 1-Naph i-Pr

te

63% 50% 98% 97% 84% 96% 41% 63% 50%

Scheme 117. Mn-catalyzed selective C–C bond cleavage in ketones with carbodiimides [163]
p
ce

The proposed catalytic cycle (Scheme 118) starts with the formation of unsaturated
hydride complex 177 either by dissociation of [(CO)4MnH]3, or, in the case of Mn2(CO)10, via
thermal Mn–Mn bond cleavage and hydrogen abstraction from dioxane (solvent) by the
Ac

radicals (CO)5Mn•.

141
Page 141 of 152
Edited June 30

O [(CO) 4MnH] 3

Ph NHp-Tol

H p-Tol
OC N . N
OH Mn CO
Tol-p
OC
Ph NTol-p CO

t
ip
177
N Tol-p
p-Tol C
OH N

cr
Ph OC CO
Mn
N
OC H

us
p-Tol N Tol-p CHO
OH
178
Ph
Tol-p Tol-p
p-Tol
.

an
N N N

p-Tol N OC CO
+ OH
Mn
.

N OC H Ph
M
CO

179
d

Tol-p
N NHTol-p
p te

p-Tol N N p-TolHN N
ce

Scheme 118. Proposed catalytic cycle for Mn-catalyzed selective C–C bond cleavage in
ketones with carbodiimides [163]
Ac

The key step of the catalytic process is a nucleophilic addition of the enol form of the
ketone to the activated carbodiimide ligand, followed by an intramolecular cyclization within
the resulting intermediate 179 to produce the four-membered cyclic azetidin-2-imine, along
with regeneration of the starting complex 177. The incipient cyclic azetidin-2-imine
undergoes a concerted ring-opening reaction to afford the enol form of the final amide
product, and a ketenimine, which react with the starting carbodiimide through a sequence of
aza-Diels-Alder and aromatization of the resulting adduct to give the quinoline byproduct.

142
Page 142 of 152
Edited June 30

Conclusion and outlook

The present literature survey provides convincing evidence that manganese
organometallic complexes are able to catalyze a broad diversity of transformations leading to
the selective formation of one or several carbon-carbon and/or carbon-heteroatom bonds,
providing in many cases a synthetic access to highly valuable organic products. To date, it
appears that only two reactions, namely the hetero-coupling of Grignard reagents [38] and the

t
ip
[2+2+2] cycloaddition of esters with terminal alkynes [109-111], are strictly specific to
manganese, but in many cases, manganese complexes have proved competitive and even

cr
superior to more traditional catalysts based on noble (Re, Ru, Rh, Pd) or readily available (Fe,
Co, Ni, Cu) transition metals in terms of catalytic activity or, more often, in terms of

us
improved chemoselectivity and/or functional group tolerance. In some cases, the utilization of
mixed-metals Mn/Cu, Mn/Ru, or Mn/Rh catalysts is beneficial, revealing a potential for future
implication of organometallic manganese complexes in the design of novel cooperative or
dual catalytic systems.

an
Though particular attention has been paid to the known mechanistic aspects of Mn-
M
catalyzed reactions, it is important to mention that only few of them, published mostly during
the last 5 years, were strongly supported by unambiguous experimental and/or theoretical
evidence. A deeper understanding of the elementary chemical steps taking place within the
d

coordination sphere of manganese, such as carbon–halogen bond activation or carbon–

te

heteroatom bond formation, will surely provide new ideas for the upgrading of the existent
and the design of novel catalytic systems. However, such a task does not seem to be very
p

simple due to the numerous oxidation and spin states available for manganese complexes
ce

bearing low and medium field ligands, which can obviously complicate a spectroscopic
detection of reaction intermediates and render theoretical studies much more time-consuming.
The great majority of reports on the use of manganese organometallic complexes in
Ac

homogeneous catalysis have been carried out with simple commercially available inorganic or
organometallic manganese precursors. This is, in fact, very similar to the parallel early
development stage of iron-based catalysis. However, very recently it was clearly
demonstrated that a rational design of the ligand environment around the manganese center is
often the key to success, as illustrated by recent seminal reports on the catalysis of ketones
hydrosilylation [14] or on electrochemical CO2 reduction [18] processes. Manganese catalysts
tailored with more sophisticated ligands, and/or subject to unconventional photochemical or
redox catalyst activation procedures, can further enlarge the existing chemist’s toolbox in the
near future, providing, in particular, efficient enantioselective transformations of pro-chiral

143
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organic molecules. We hope that this review article will contribute to break the long-standing
paradigm about the supposedly purely fundamental character of manganese organometallic
chemistry, thus paving the way to extensive investigations in the prospect of applied Mn-
based homogeneous catalytic systems. Taking into account the availability, safety and
extremely rich reactivity of manganese precursors, these have a chance to reach the same
level of success as iron-, cobalt-, nickel- and copper-based catalytic systems.

t
ip
Acknowledgements

cr
Financial support from CNRS is gratefully acknowledged. D.A.V. also thanks the IDEX-
UNITI for a starting grant. We are grateful to all researchers contributed to the development

us
of catalytic applications for organometallic manganese complexes.

an
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