Organic Chemistry

6th Edition
Paula Yurkanis Bruice

Chapter 5
Stereochemistry

The Arrangement of
Atoms in Space;
The Stereochemistry of
Addition Reactions

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 Isomers
Non-identical compounds having the
same molecular
formula

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Cis-Trans Isomers in Alkenes and Rings

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An Asymmetric Center Is a Cause of Chirality

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A stereocenter (or stereogenic center) is an atom at
which the interchange of two groups produces a
stereoisomer

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•Achiral compounds have superimposable mirror images.
•Chiral compounds have nonsuperimposable mirror images.

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Common Objects Also Exhibit
Chirality or Achirality

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 Using the -Plane to Determine if a
Molecule is Chiral or Achiral
• The -plane is an internal plane of symmetry passing
through a molecule.
• If there is one or more -planes, the molecule is achiral.
• If there are no -planes, the molecule is chiral.

The presence of
asymmetric centers
does not imply chirality!
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Drawing Enantiomers

Perspective
formula

Fischer
projection
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 Naming Enantiomers
The R,S system of nomenclature

Rank the groups (atoms) bonded to the asymmetric center.

Ranking Rules:
1. Consider the atomic number of the
atoms bonded directly to the asymmetric
carbon.
2. If there is a tie, consider the atoms
attached to the tied atoms.
3. Multiple bonds are treated as
attachment of multiple single bonds using
“divide-duplicate.”
4. Rank the priorities by mass number in
isotopes.
Same rules as for E/Z
assignments

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Orient the lowest priority (4) away from you:

• Clockwise = R configuration
• Counterclockwise = S configuration

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Naming from the Perspective Formula
1. Rank the groups bonded to the asymmetric center with
the lowest priority group in the back.

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2. If the group (or atom) with the lowest priority is in the
front, assign S or R and then switch your answer to R
or S respectively.

Configuration is S

3. Alternatively, atoms or groups can be switched so as

to place the lowest priority group in the back. One
switch: configuration opposite; two switches,
configuration unchanged.

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 Configuration from the Fischer Projection
1. Consider the 3-dimensional equivalent to the Fischer
Projection.

2. Rank the groups (or atoms) that are bonded to the

asymmetric center and then draw an arrow from the highest
priority (1) to the next highest priority (2).

Lowest priority
group in back

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3. If the lowest priority is on a horizontal bond, the
configuration is opposite to the direction of the arrow.
Lowest priority
group in front

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 D and L Nomenclature
• Emil Fischer originally used Fischer Projections to show the
stereochemistry of amino acids and carbohydrates.
• These Fischer Projections have carbons on the vertical axis
and Hs and OH or NH2 groups on the horizontal axis.

D, because
L, because hydroxyl is on
amine is on the the right
left

• Commercial protein supplements have “L-glycine” as an ingredient. Is this

nomenclature correct?
• Most chiral amino acids have the S configuration. Which one has the R
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Discrimination of Enantiomers by
Biological Molecules
Three-Point Binding:

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Chiral Drugs Interacting with a
Chiral Receptor

The unnatural epinephrine enantiomer has the amine and

hydroxyl groups reversed. Therefore no receptor binding.
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Influence of Chirality on Drug Action

Enantiomers can have different drug activity

because of different receptor binding activity.

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 Chiral compounds are optically active; they rotate the

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plane of polarized light.

Clockwise (+) Counterclockwise (-)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized
light. They are optically inactive.
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 A polarizer measures the degree of optical rotation of a compound

x
The observed rotation (a):

Specific Rotation

•T is the temp in °C
• is the wavelength
• is the measured rotation in degrees
•l is the path length in decimeters
•c is the concentration in grams per mL
Each optically active compound has a characteristic specific rotation.
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 X
• A racemic mixture, which contains an equal amount of the
two enantiomers, is optically inactive.

• The enantiomeric excess (ee) tells us how much of an excess

of one enantiomer is in a mixture.

observed specific rotation

enantiomeric excess = x 100%
specific rotation of the
pure enantiomer

2-Bromobutane, Four possibilities:

• (S) - (+) - 2 – Bromobutane, a = + 23.1o

• (R) - (-) - 2 – Bromobutane, a = + 23.1o

• 2 – Bromobutane, racemic, zero rotation

• An enantiomeric excess
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Isomers with more than one asymmetric center: a
maximum of 2n stereoisomers can be obtained

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Diastereomers are stereoisomers that are not enantiomers 0

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Identification of Asymmetric Carbons
in Cyclic Compounds

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1-Bromo-4-methylcyclohexane has only one cis isomer
and one trans isomer

These compounds possess an internal plane of

symmetry ( -plane) and are therefore achiral.

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 Meso Compounds
Have two or more asymmetric centers and an internal plane
of symmetry ( -plane)

Meso compounds are achiral molecules with

asymmetric centers
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If a compound with two asymmetric centers has the same
four groups bonded to each of the centers, one of its
stereoisomers will be a meso compound

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-Plane Present: No -Plane Present:

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As long as any one conformer of a compound has a
plane of symmetry, the compound will be achiral

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 Asymmetric Nitrogen Centers
Rapid lone pair inversion prevents resolution of
amine enantiomers:

Quaternary amine-based enantiomers can be resolved

because there is no lone pair:

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Asymmetric Sulfur and Phosphorus
Centers
Lone pair inversion does not occur and enantiomers
are resolvable

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 Naming Isomers with More Than One Asymmetric Center

The OH group at C-2 has the highest priority,

followed by Br in C-3

The isomer is named (2S, 3R)-3-bromo-2-butanol

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When Fisher projections are used…

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A regioselective reaction: preferential formation of one
constitutional isomer:

A stereoselective reaction: preferential formation of a

stereoisomer:

• Enantioselectivity: selective formation of

an enantiomer
• Diastereoselectivity: selective formation
of a diastereomer

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A stereospecific reaction: each stereoisomeric reactant
forms a different stereoisomeric product or a different
set of stereoisomeric products

•All stereospecific reactions are stereoselective

•Not all stereoselective reactions are stereospecific

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 Predicting the Stereochemical Result of
Reactions □
• An achiral or a racemic product results from achiral
reactants and reagents:
Excess of an
enantiomer not
observed

Excess of an
enantiomer not
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• The formation of a product in enantiomeric excess from
an achiral or racemic reactant requires an
enantioselective catalyst:

Used to distinguish
treated from untreated sewage

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• The presence of an asymmetric center near a reacting
center will result diastereoselectivity.

Diastereomers formed in
unequal amounts

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• No reaction at the asymmetric center; both the reactant and the
product have the same relative configuration.

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• If a reaction breaks a bond at the asymmetric center, you
need to know the reaction mechanism in order to predict the
configuration of the product.

•SN1 Reaction: racemization

•SN2 Reaction: inversion of configuration

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 Stereochemistry of Electrophilic
Addition Reactions of Alkenes
A regioselective reaction without stereoselectivity

Racemic
Mixture
Results

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Addition reactions that form products with two
asymmetric centers

All four possible stereoisomers result:

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The Stereochemistry of Hydrogen Addition

Exclusive Formation of Erythro Enantiomers:

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Exclusive Formation of Meso Stereoisomer:

Exclusive Formation of Threo Enantiomers:

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 Addition of H2 to cyclic alkene

Racemic Mixture:

Meso:

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 The Stereochemistry of Epoxidation
The addition of a peroxyacid to an alkene to form an epoxide
is a concerted reaction. Orientation of alkyl substituents
remain unchanged.

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 The Stereochemistry of
Hydroboration–Oxidation

Syn addition
of H2O

Regioselective:
Syn addition
OH on least
substituted carbon of H2O

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The Stereochemistry of Bromination

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Exclusive Formation of Threo Enantiomers from
cis Alkenes:

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Exclusive Formation of Erythro Enantiomers from
trans Alkenes:

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Stereochemistry of Alkene Addition
Reactions

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Enzyme Catalyzed Reactions Are
Enantioselective

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 Enzyme Catalyzed Reactions Are
Enantioselective

Used for the kinetic resolution of enantiomers:

Enantiomers react at
different rates in the
presence of a chiral
catalyst.

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 Resolution of a Racemic Mixture
(S)-base
(R)-acid (S)-acid (R,S)-salt (S,S)-salt
enantiomers diastereomers

The base is typically an alkaloid:

(R,S)-salt (S,S)-salt

HCl HCl

(S)-baseH+ (S)-baseH+
+ +

(R)-acid (S)-acid

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