Stereoisomerism

and Chirality

3-1

Isomers
Nonidentical compounds having the same molecular
formula

3-2

Isomers

Isomers: different compounds with the same

molecular formula
Constitutional isomers: isomers with a different
connectivity
Stereoisomers: isomers with the same
connectivity but a different orientation of their
atoms in space

3-3

Are the following pairs of compounds consitutional

isomers or stereoisomers?
a)
constitutional

b)
constitutional

c)

stereoisomer

3-4

Chirality

Chiral: from the Greek, cheir, hand

an object that is not superposable on its mirror image

Achiral: an object that lacks chirality; one that

lacks handedness
an achiral object has at least one element of symmetry
plane of symmetry: an imaginary plane passing
through an object dividing it so that one half is the
mirror image of the other half
center of symmetry: a point so situated that identical
components are located on opposite sides and
equidistant from that point along the axis passing
through it
3-5

Elements of Symmetry

Symmetry in objects

3-6

Elements of Symmetry

Plane of symmetry (contd)

mirror
plane

HO

OH

3-7

Chiral Center

The most common (but not the only) cause of

chirality in organic molecules is a tetrahedral
atom, most commonly carbon, bonded to four
different groups
A carbon with four different groups bonded to it
is called a chiral center
all chiral centers are stereocenters, but not all
stereocenters are chiral centers (see Figure 3.5)

Enantiomers: stereoisomers that are

nonsuperposable mirror images
refers to the relationship between pairs of objects
3-8

A stereocenter (stereogenic center) is an atom at which

the interchange of two groups produces a stereoisomer

3-9

Enantiomers

2-Butanol
has one chiral center
here are four different representations for one
enantiomer
OH

C H
H3 C
CH2 CH3
(1)

H OH

H3 C

C
CH2CH3
(2)

H OH

OH

(3)

(4)

using (4) as a model, here are two different

representations
for the OH
enantiomer
OH
OHof (4)
(4)

representations for the

enantiomer of (4)
3-10

3-11

Enantiomers

The enantiomers of lactic acid

drawn in two different representations
O

OH

HO

H
CH3

OH

HO

O
OH

OH

H
CH3

HO
OH

3-12

Enantiomers

2-Chlorobutane

Cl

CH3 CHCH2 CH3

H Cl

Cl H

3-13

Enantiomers

3-Chlorocyclohexene
Cl

Cl

3-14

Enantiomers

A nitrogen chiral center

+

N
H3 C

N
CH2 CH3

CH3 CH2 CH3

A pair of enantiomers

3-15

R,S Convention

Priority rules
1. Each atom bonded to the chiral center is assigned a
priority based on atomic number; the higher the
atomic number, the higher the priority
(1)

(6)

(7)

(8)

(16)

(17)

(35)

(53)

-H

-CH3

-NH2

-OH

-SH

-Cl

-Br

-I

Increasing priority

2. If priority cannot be assigned per the atoms bonded to

the chiral center, look to the next set of atoms; priority
is assigned at the first point of difference
(1)

-CH2 -H

(6)

-CH2 -CH3

(7)

-CH2 -NH2

(8)

-CH2 -OH

Increasing priority

3-16

R,S Convention
3. Atoms participating in a double or triple bond are
considered to be bonded to an equivalent
number of similar atoms by single bonds
-CH=CH2
O
-CH

is treated as
is treated as

-CH-CH2
O C
C

H
C CH

is treated as

C C
C C H
C C

3-17

Naming Chiral Centers

1. Locate the chiral center, identify its four substituents, and assign
priority from 1 (highest) to 4 (lowest) to each substituent
2. Orient the molecule so that the group of lowest priority (4) is
directed away from you
3. Read the three groups projecting toward you in order from
highest (1) to lowest priority (3)
4. If the groups are read clockwise, the configuration is R; if they are
read counterclockwise, the configuration is S
H Cl

(S)-2-Chlorobutane

S
2

3-18

Naming Chiral Centers

(R)-3-Chlorocyclohexene
Cl

H
2

(R)-Mevalonic acid
1

1 4
HO CH3 O
HO

OH

3-19

Enantiomers & Diastereomers

For a molecule with 1 chiral center, 21 = 2

stereoisomers are possible
For a molecule with 2 chiral centers, a maximum
of 22 = 4 stereoisomers are possible
For a molecule with n chiral centers, a maximum
of 2n stereoisomers are possible

3-20

Enantiomers & Diastereomers

2,3,4-Trihydroxybutanal
two chiral centers
22 = 4 stereoisomers exist; two pairs of enantiomers
CHO

CHO

OH HO

OH HO

CH2 OH

CH2 OH

A pair of enantiomers
(Erythreose)

CHO

CHO

OH HO

HO

OH

CH2 OH

CH2 OH

A pair of enantiomers
(Threose)

Diastereomers:

stereoisomers that are not mirror images

refers to the relationship among two or more objects

3-21

Enantiomers & Diastereomers

2,3-Dihydroxybutanedioic acid (tartaric acid)

two chiral centers; 2n = 4, but only three stereoisomers exist
COOH

COOH

OH HO

OH HO

COOH

COOH

A meso compound
(plane of symmetry)

COOH

COOH

OH HO

HO

OH

COOH

COOH

A pair of enantiomers

Meso compound: an achiral compound possessing

two or more chiral centers that also has chiral isomers
3-22

Fischer Projections

Flat representation of a 3-D molecule.

A chiral carbon is at the intersection of horizontal
and vertical lines.
Horizontal lines are forward, out-of-plane.
Vertical lines are behind the plane.

3-23

Fischer Projections (Continued)

3-24

Fischer Rules

Carbon chain is on the vertical line.

Highest oxidized carbon is at top.
Rotation of 180 in plane doesnt change
molecule.
Do not rotate 90!

3-25

180 Rotation

A rotation of 180 is allowed because it will not change

the configuration.

3-26

90 Rotation

A 90 rotation will change the orientation of the horizontal

and vertical groups.
Do not rotate a Fischer projection 90.

3-27

Fischer Mirror Images

Fisher projections are easy to draw and make it

easier to find enantiomers and internal mirror
planes when the molecule has 2 or more chiral
centers.

CH3
H

Cl

Cl

H
CH3
3-28

Fischer (R) and (S)

Lowest priority (usually H) comes forward, so

assignment rules are backwards!
Clockwise 1-2-3 is (S) and counterclockwise 1-2-3
is (R).
Example:
CH3

(S)

Cl

Cl

(S)

CH3
3-29

Diastereomers

Molecules with two or more chiral carbons.

Stereoisomers that are not mirror images.

3-30

Enantiomers & Diastereomers

2-Methylcyclopentanol
CH3 OH

HO H3 C

H
H
H
H
cis-2-Methylcyclopentanol
(a pair of enantiomers)
CH3 H

diastereomers

H H3 C

H
OH
H
HO
trans-2-Methylcyclopentanol
(a pair of enantiomers)

3-31

Enantiomers & Diastereomers

1,2-Cyclopentanediol
OH HO

OH HO

H
H
H
H
cis-1,2-Cyclopentanediol
(a meso compound)
OH

diastereomers

HO

OH H
H HO
trans1,2-Cyclopentanediol
(a pair of enantiomers)

3-32

Enantiomers & Diastereomers

cis-3-Methylcyclohexanol
H3 C

OH HO

CH3

3-33

Enantiomers & Diastereomers

trans-3-Methylcyclohexanol
H3 C

CH3
OH HO

3-34

Isomers
rotation about
single bonds

Compounds with the

same molecular formula
same
connectivity

different
connectivity

Cis,Trans
(E,Z) Isomers
(can be called
diastereomers)

rotation
restricted

Constitutional
Isomers

Stereoisomers
stereoisomers
but no chiral centers

Conformations

Conformational
Isomers

with chiral centers

m ore than
one chiral center
achiral

Meso
Compounds

Atropisomers
one chiral center

chiral

not mirror
images
Diastereomers

mirror
images

Enantiomers

Enantiomers

3-35

Properties of Stereoisomers

Enantiomers have identical physical and

chemical properties in achiral environments
Diastereomers are different compounds and have
different physical and chemical properties
meso tartaric acid, for example, has different physical
and chemical properties from its enantiomers (see
Table 3.1)

3-36

Plane-Polarized Light

Ordinary light: light vibrating in all planes

perpendicular to its direction of propagation
Plane-polarized light: light vibrating only in
parallel planes
Optically active: refers to a compound that
rotates the plane of plane-polarized light

3-37

Plane-Polarized Light
plane-polarized light is the vector sum of left and right
circularly polarized light
circularly polarized light reacts one way with an R
chiral center, and the opposite way with its enantiomer
the result of interaction of plane-polarized light with a
chiral compound is rotation of the plane of polarization

3-38

Plane-Polarized Light

Polarimeter: a device for measuring the extent of

rotation of plane-polarized light

3-39

Optical Activity
observed rotation: the number of degrees, , through
which a compound rotates the plane of polarized light
dextrorotatory (+): refers to a compound that rotates
the plane of polarized light to the right
levorotatory (-): refers to a compound that rotates of
the plane of polarized light to the left
specific rotation: observed rotation when a pure
sample is placed in a tube 1.0 dm in length and
concentration in g/mL (density); for a solution,
concentration is expressed in g/ 100 mL
COOH
C

H
H3 C
OH
(S)-(+)-Lactic acid
21
[]D = +2.6

COOH

H C
CH3
HO
(R)-(-)-Lactatic acid
21
[]D = -2.6

3-40

Optical Purity

Optical purity: a way of describing the

composition of a mixture of enantiomers
Percent optical purity =

[ ]sam ple

[]pure enantio mer

x 100

Enantiomeric excess: the difference between the

percentage of two enantiomers in a mixture
[R] - [S]
x 100 = %R - %S
Enantiomeric excess (ee) =
[R] + [S]

optical purity is numerically equal to enantiomeric

excess, but is experimentally determined
3-41

Enantiomeric Excess
Example: a commercial synthesis of naproxen, a
nonsteroidal anti-inflammatory drug (NSAID), gives the S
enantiomer in 97% ee
CH3

COOH
H3 CO

(S)-Naproxen

Calculate the percentages of the R and S enantiomers in

this mixture

3-42

Resolution

Racemic mixture: an equimolar mixture of two

enantiomers
because a racemic mixture contains equal numbers of
dextrorotatory and levorotatory molecules, its specific
rotation is zero

Resolution: the separation of a racemic mixture

into its enantiomers

3-43

Resolution

One means of resolution is to convert the pair of

enantiomers into two diastereomers
diastereomers are different compounds and have
different physical properties

A common reaction for chemical resolution is

salt formation
+
:B
RCOOH
(R,S)-Carboxylic (R)-Base
acid

RCOO HB

(R,R)-Salt + (S,R)-Salt)

after separation of the diastereomers, the

enantiomerically pure acids are recovered

3-44

Resolution
racemic acids can be resolved using commercially
available chiral bases such as 1-phenylethanamine
NH2

(S)-1-Phenylethanamine

NH2

(R)-1-Phenylethanamine

racemic bases can be resolved using chiral acids such

as OH O
H3C CH3
O
HO

OH

HO

OH

HOOC

COOH

CH3
OH
O OH
(2R,3R)-(+)-Tartaric acid (S)-(-)-Malic acid (1S,3R)-(+)-Camphoric acid
O

3-45

Amino Acids
the 20 most common amino acids have a central
carbon, called an -carbon, bonded to an NH2 group
and a COOH group
in 19 of the 20, the -carbon is a chiral center
18 of the 19 -carbons have the R configuration, one
has the S configuration
in the D,L system, all have the L configuration
at neutral pH, an amino acid exists as an internal salt
in this structural formula, the symbol R = a side chain
side chain

H3 N

O-

R
Ionized or zwitterion
form of an amino acid

3-46