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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
Lowest priority
arrow.
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.
An L-Amino Acid
_
L, because
amine is on
the left
+
H3N
A D-sugar
O
COO
H
H
R
H
OH
D, because
hydroxyl is on
the right
OH
• 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
configuration?
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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
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
a  =
T
The observed rotation (a):
a   Specific Rotation
T
a
lc
•T is the temp in °C
• is the wavelength
•a 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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• 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
x 100%
enantiomeric excess =
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
Diastereomers are stereoisomers that are not enantiomers
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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
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Excess of an
enantiomer not
observed
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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:
OH on least
substituted carbon
Syn addition
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
(R)-acid
(S)-acid
enantiomers
(S)-base
(R,S)-salt (S,S)-salt
diastereomers
The base is typically an alkaloid:
(R,S)-salt (S,S)-salt
HCl
HCl
(S)-baseH+ (S)-baseH+
+
+
(S)-acid
(R)-acid
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