Stereochemistry: structural

and geometric isomerism

Fabio Andrés Castellanos Castillo

1
3

2
 Review of Isomerism

 Isomers – Different compounds that have

the same molecular formula.
 Constitutional Isomers – differ because
their atoms are connected in a different
order.

CH3CH2-O-CH2CH3 vs. CH3CH2CH2CH2OH

 Review of Isomerism
 Conformational Isomers – differ because of
rotation about single bonds (can
interconvert).

CH3 Br

Br CH3
Review of Isomerism
 Configurational Isomers – differ in the
arrangement of their atoms in space (cannot
interconvert).

H H H CH3
C C C C
H3C CH3 H3C H
cis-2-butene trans-2-butene
Review of Isomerism
 Configurational Isomers – differ in the
arrangement of their atoms in space (cannot
interconvert).

H H H Cl

Cl Cl Cl H
cis-1,3-dichlorocyclopentane trans-1,3-dichlorocyclopentane
 Isomerism

 Isomerism – The phenomenon whereby

certain chemical compounds have structures
that are different although the compounds
possess the same elemental composition.

 Isomers – Two or more chemical substances

having the same elementary composition and
molecular weight but differing in structure.
 Isomerism
 Example C4H10
H
H H H H H H
H C H
H C C C C H
H C C C H
H H H H
H H H
n-Butane Isobutane

These structures are constitutional isomers

These structures are stereoisomers
 Isomerism

Constitutional isomers Stereoisomers

Different bond sequences, atoms Same bond sequences but different

are connected differently. spatial orientation of the atoms

Chain
Geometric isomers
Position
Enantiomers and diastereoisomers
Function
 Chain isomers

 It change in the disposition of the carbon atoms

or carbon skeleton, it means, the structure could
be lineal or branched.
 Isomers of position
 Is one in which the compounds have the same
carbon skeleton but in which the functional
group or substituent occupies different position
 Isomers of function

 Is one in which the functional group varies, but

the carbon skeleton is preserved

The C3H6O may have the isomers:

This isomerism can occur between some related

functional groups such as alcohols and ethers;
acid and esters; aldehydes and ketones
Constitutionals Isomers
 Exercise:

Draw the next structures:

Two isomers with C2H7N

Five isomers with C6H14
Two isomeric esters with C5H10O2

H3C H3C NH
NH2 CH3
CH3
H3C H3C H3C
H3C H3C
O CH3 CH3 H3C CH3
O O CH3
CH3
O CH3
H3C CH3 H3C
H3C CH3
CH3 H3C
 Constitutional isomers

Different bond sequences, it means atoms

are connected differently.

Chain Position Function

Same function Different
lineal or
but different functional
branched
position gropus
 Exercise: say which of the next couples are chain, position
and functional isomers

H3C CH3 H3C

CH3 H3C CH3

H3C O O
H3C
CH3
CH3
O H3C

HO CH3 O OH
Exercise

Stablish one chain isomer, one position isomer and one position isomer for
each molecular formula:
 Isomerism
Chain
STRUCTURAL Position
Function

ISOMERS

CONFORMATIONAL (Stereoisomers produced by rotation of simple

bonds)

SPATIAL GEOMETRIC
(Diastereomers cis/trans –
CONFIGURATIONAL E/Z)

OPTICAL
(Enantiomers/
Diastereomers/meso)
CONFORMATION
CONFORMATION: The different arrangements of atoms that result from
bond rotation are called conformations.
CYCLOHEXANE
 Stereoisomers

Same bond sequences but different spatial

orientation of the atoms

Geometric Function
Cis, trans, E, Z
Optical Isomers
Isomers
 GEOMETRIC ISOMERS

1. Are configurational isomers that differ in the spatial position of substituents

around double bond. It is needed two different functional groups at each end
of the double bond

Cis: with the two biggest substituents in the same side

Trans: with the two biggest substituents in opposites positions
 GEOMETRIC ISOMERS

2. Cycloalkanes are less flexible than open-chain alkanes. Because of their

cyclic structures, cycloalkanes have two faces, then its possible say that if two
substituents are oriented to the same face, they will have cis position, and if
they are oriented to opposite faces, they will have a trans position.

Cis: with the two biggest substituents in the same side

Trans: with the two biggest substituents in opposite positions
 OPTICAL ISOMERS

When compounds have at least one atom with four different substituents, can
be formed two different varieties called optical isomers, enantiomers or chiral
forms.
 Asymmetric carbon or chiral: is the one who will unite
four different groups

 Chiral Compounds: are compounds having at least one

asymmetric center and whose structure is not
superimposable
 Stereoisomerism
 Another kind of configurational isomerism.
 Chiral – Nonsuperimposable on its mirror

image.
 Achiral – Superimposable on its mirror image.
 If a molecule (or object) has a mirror plane or

an inversion center, it cannot be chiral.

Chiral or Achiral?
 Hammer
Chiral or Achiral?
 Hammer

achiral
Chiral or Achiral?
 Brandy snifter
Chiral or Achiral?
 Brandy snifter

achiral achiral
Chiral or Achiral?
 Shears
Chiral or Achiral?
 Shears

chiral
Chiral or Achiral?
 Beer mug
Chiral or Achiral?
 Beer mug

achiral
Chiral or Achiral?
 Hiking boot
Chiral or Achiral?
 Hiking boot

chiral
Chiral or Achiral?
 Baseball glove
Chiral or Achiral?
 Baseball glove

chiral
Chiral or Achiral?
 Boat propeller
Chiral or Achiral?
 Boat propeller

chiral
Chiral or Achiral?
 Desk chair
Chiral or Achiral?
 Desk chair

achiral
Chiral or Achiral?
 School desk
Chiral or Achiral?
 School desk

chiral
Chiral or Achiral?
 cis-1,3-dimethylcyclopentane
 Chiral or Achiral?
 cis-1,3-dimethylcyclopentane

mirror plane
 Chiral or Achiral?
 cis-1,3-dimethylcyclopentane

achiral

mirror plane
Chiral or Achiral?
 trans-1,3-dimethylcyclopentane
Chiral or Achiral?
 trans-1,3-dimethylcyclopentane

chiral
 Chiral or Achiral?
 1,1-dimethylcyclohexane
Chiral or Achiral?
 1,1-dimethylcyclohexane

achiral
Chiral or Achiral?
 2-butanol
Chiral or Achiral?
 2-butanol

mirror image
Copyright © 2010 Pearson
Education, Inc.
Chiral or Achiral?
 2-butanol

chiral mirror image

Copyright © 2010 Pearson
Education, Inc.
Chiral or Achiral?
 2-butanol Asymmetric
center

chiral mirror image

Chiral or Achiral?
 2-butanone
Chiral or Achiral?
 2-butanone

achiral
Chiral or Achiral?
 2-bromopropane
Chiral or Achiral?
 2-bromopropane

achiral
Compounds which specular image is superimposable are identical
(homomerics) and no enantiomers

CH3 H3C

CH3 H3C
H3C CH3

H3C
= CH3

Br Br
Stereoisomerism
 A chiral compound and its mirror image are
called enantiomers.
 2-butanol:
Stereoisomerism
 A chiral compound and its mirror image are
called enantiomers.
 2-butanol:

enantiomers
Stereoisomerism
 Asparagine:

O OH HO O
C C

H2N C H H C NH2

CH2 CH2
C C
H2N O O NH2
Stereoisomerism
 Asparagine: mirror
plane

O OH HO O
C C

H2N C H H C NH2

CH2 CH2
C C
H2N O O NH2
L-asparagine (from
asparagus) bitter
taste
Stereoisomerism
 Asparagine: mirror
plane

O OH HO O
C C

H2N C H H C NH2

CH2 CH2
C C
H2N O O NH2
L-asparagine (from D-asparagine (from
asparagus) bitter vetch) sweet taste
taste
Stereoisomerism
 Asparagine: mirror
plane

O OH HO O
C C

H2N C H H C NH2

CH2 CH2
C C
H2N O O NH2
L-asparagine (from D-asparagine (from
asparagus) bitter vetch) sweet taste
taste

enantiomers
Stereoisomerism
 Camphor:

O O

enantiomers
 ASIGNACIÓN DE LA CONFIGURACIÓN
ABSOLUTA
1 2

3
Nature Chemical Biology 3, 408 - 414 (2007)
Absolute Configuration
 R and S
 Look down the bond from the chiral carbon to
the smallest group:

CH 2CH3 1 2
OH HO CH2CH3
H C = C
CH3 CH3
3
Absolute Configuration
 R and S
 Look down the bond from the chiral carbon to
the smallest group:

CH 2CH3 1 2
OH HO CH2CH3
H C = C
CH3 CH3
3
Absolute Configuration
 R and S
 Assign priorities to the remaining groups
based on atomic numbers.
 Clockwise (highest to lowest priority)  R
 Counterclockwise  S

CH 2CH3 1 2
OH HO CH2CH3
H C = C
CH3 CH3
3
Absolute Configuration
 R and S
 Assign priorities to the remaining groups
based on atomic numbers.
 Clockwise (highest to lowest priority)  R
 Counterclockwise  S

CH 2CH3 1 2
OH HO CH2CH3
H C = C
CH3 CH3
3

(R)-2-butanol
Absolute Configuration
 Assign priority:
 Atomic number of atom directly bonded.
 If the same atom is bonded, go to the next
atom, etc.
 Groups containing multiple bonds are treated
as though multiple atoms were attached:

N C
C O = C O C N = C N
O C N C
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:

3 1
H3C 4 F 4
H H
C C
Cl CH
Br S 2 D R 2 3
1 3

2 O
(CH3)2CHCH2 4
1
H
H C 4
C H

S Cl C
CH3CH2CH2CH2 1 C N
3 CH3CH2 R 2
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
Absolute Configuration
 Determine the absolute configuration of the
following compounds:
CH3 CH3
1 2
CH3O CH 4 CH3O CH 4
H H
C C
2
S CH3 1
R CH3
CH3CH2 CH 3 CH3CH2 CH 3

OH OCH3
1 2
CH2=CH 4 CH2=CH 4
H H
C C
2
S CH3 C CH
CH3CH2 3 (CH3)2CH S 1
3
 Properties of the stereoisomers
H OH HO H
H O
-D-glucosa O H -L-glucosa
HO OH
punto fusión 146 HO OH punto fusión 146
enantiómeros HO OH
D H OH H
HO D
H H H H

H OH
H O -D-glucosa
HO punto fusión 148-155
HO H
H D
OH
H OH

Enantiomers Diasteroisomers
Physics properties (density, Peb, Pf etc) y
thermodynamics (DG, DH, DS etc) are Physics properties (densidad, Peb, Pf etc)
identical. and y thermodynamics (DG, DH, DS etc)
Interaction with the polarized light is are different.
opposite.
Spectra NMR, UV/VIS, IR etc son idénticos. Spectra NMR, UV/VIS, IR etc, are different.
DRO, CD are opposite.
Optical Activity
 Enantiomers cannot be distinguished based
on physical properties such as boiling points,
melting points, or densities.
 However—when plane-polarized light is
passed through a solution of one of the
enantiomers, the plane of polarization is
rotated:
Optical Activity
 The enantiomer that rotates the plane of
polarized light in a clockwise direction is
called dextrorotatory and is called the (+)-
enantiomer.
 The other enantiomer (counterclockwise
rotation) is levorotatory, the (-)-enantiomer.
 Racemic Mixture: A 50:50 mixture of two
enantiomers – no optical rotation!
Optical Activity
 The enantiomer that rotates the plane of
polarized light in a clockwise direction is
called dextrorotatory and is called the (+)-
enantiomer.
 The other enantiomer (counterclockwise
rotation) is levorotatory, the (-)-enantiomer.
 Racemic Mixture: A 50:50 mixture of two
enantiomers – no optical rotation!
Optical Activity
 The enantiomer that rotates the plane of
polarized light in a clockwise direction is
called dextrorotatory and is called the (+)-
enantiomer.
 The other enantiomer (counterclockwise
rotation) is levorotatory, the (-)-enantiomer.
 Racemic Mixture: A 50:50 mixture of two
enantiomers – no optical rotation!
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro
These two compounds are mirror images.
diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
CH3 CH3 H
H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
CH3 CH3 H
H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Note that the absolute configuration for both
Cl asymmetric centers is different. Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro
The absolute configuration
diastereomers for diastereomers
one of the asymmetric diastereomers
centers is different, the
other is the same.
Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2-chloro-3-iodobutane
H
CH3 Cl Cl H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2S,3R)-2-chloro-3-iodobutane (2R,3S)-2-chloro-3-iodobutane
erythro erythro

diastereomers diastereomers diastereomers

Cl Cl
CH3 H H CH3
C C enantiomers C C
I I
H CH3 CH3 H
(2R,3R)-2-chloro-3-iodobutane (2S,3S)-2-chloro-3-iodobutane
threo threo
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers
Both asymmetric centers are different.
H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers One of the asymmetric centers is different.

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 One of CH
CH3 Cl 3
the asymmetric centers is different.
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers
Mirror plane!
H CH3 CH3
CH3 Cl This diastereomer is
C C = C C achiral!
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 2,3-dichlorobutane
Cl Cl
CH3 H H CH3
C C enantiomers C C
Cl Cl
H CH3 CH3 H
(2R,3R)-2,3-dichlorobutane (2S,3S)-2,3-dichlorobutane
threo threo
diastereomers
diastereomers

H CH3 CH3
CH3 Cl
C C = C C
Cl Cl Cl
H CH3
H H
(2R,3S)-2,3-dichlorobutane meso
Compounds with Two Asymmetric Centers
 Erythrose
O CHO CHO
OH
H C H H C OH H C OH
C C = =
H C OH H C OH
H
CH2OH
HO CH2OH CH2OH
Compounds with Two Asymmetric Centers
 Erythrose
O CHO CHO
OH
H C H H C OH H C OH
C C = =
H C OH H C OH
H
CH2OH
HO CH2OH CH2OH
Fischer projection
of D-erythrose
Compounds with Two Asymmetric Centers
 Erythrose
O CHO CHO
OH
H C H H C OH H C OH
C C = =
H C OH H C OH
H
CH2OH
HO CH2OH CH2OH
Fischer projection
of D-erythrose

 If the substituents are eclipsed in the Fischer

projection, it is the erythro diastereomer.
Compounds with Two Asymmetric Centers
 Threose
O CHO CHO
OH
H C H HO C H HO C H
C C = =
H C OH H C OH
HO CH2OH
H CH2OH CH2OH
Fischer projection
of D-threose

 If the substituents are not eclipsed in the Fischer

projection, it is the threo diastereomer.
Compounds with Two Asymmetric Centers
 (-)-Ephedrine
CH3 C6H5
HN H HO C H
C =
C CH3 CH3NH C H
H OH CH3
Compounds with Two Asymmetric Centers
 (-)-Ephedrine
CH3 C6H5
HN H HO C H
C =
C CH3 CH3NH C H
H OH CH3

A component of “Ma Huang”

(Ephedra sinica)
Compounds with Two Asymmetric Centers
 (-)-Ephedrine
CH3 C6H5
HN H HO C H
C =
C CH3 CH3NH C H
H OH CH3
Erythro diastereomer

A component of “Ma Huang”

(Ephedra sinica)
Compounds with Two Asymmetric Centers
 (-)-Ephedrine
CH3 C6H5
HN H HO C H
= R
C CH3NH C H
C CH3 S
H OH CH3
Erythro diastereomer

A component of “Ma Huang”

(Ephedra sinica)
Compounds with Two Asymmetric Centers
 (+)-Pseudoephedrine
CH3 C6H5
HN H H C OH
C =
C CH3 CH3NH C H
HO H CH3
Compounds with Two Asymmetric Centers
 (+)-Pseudoephedrine
CH3 C6H5
HN H H C OH
C =
C CH3 CH3NH C H
HO H CH3

The active ingredient in the

decongestant Sudafed®
Compounds with Two Asymmetric Centers
 (+)-Pseudoephedrine
CH3 C6H5
HN H H C OH
C =
C CH3 CH3NH C H
HO H CH3
Threo diastereomer

The active ingredient in the

decongestant Sudafed®
Compounds with Two Asymmetric Centers
 (+)-Pseudoephedrine
CH3 C6H5
HN H H C OH
= S
C CH3NH C H
C CH3 S
HO H CH3
Threo diastereomer

The active ingredient in the

decongestant Sudafed®
Threonine
CH3 CH CH CO2H
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.
CO2H CO2H CO2H CO2H
H C NH2 H2N C H H C NH2 H2N C H

HO C H H C OH H C OH HO C H
CH3 CH3 CH3 CH3

 Identify which are enantiomers and which are

diastereomers.
Threonine
CH3 CH CH CO2H an amino acid (one of the
building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.
CO2H CO2H CO2H CO2H
H C NH2 H2N C H H C NH2 H2N C H

HO C H H C OH H C OH HO C H
CH3 CH3 CH3 CH3

 Identify which are enantiomers and which are

diastereomers.
Threonine an amino acid (one of the
CH3 CH CH CO2H building blocks of proteins)
HO NH2
 Indicate the asymmetric carbons in threonine.
 Draw all of the stereoisomers of threonine.
CO2H CO2H CO2H CO2H
H C NH2 H2N C H H C NH2 H2N C H

HO C H H C OH H C OH HO C H
CH3 CH3 CH3 CH3
D-threonine L-threonine D-allothreonine L-allothreonine
The only one that works
for building proteins

 Identify which are enantiomers and which are diastereomers

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

Ribose

HOCH2 O OH a sugar unit in ribonucleic

acid (RNA)
H H
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

 Assign absolute configurations to each of the
asymmetric carbon atoms.
Ribose

HOCH2 O R
OH a sugar unit in ribonucleic
R acid (RNA)
H H
R R
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

 Assign absolute configurations to each of the
asymmetric carbon atoms.
Ribose

HOCH2 O R
OH a sugar unit in ribonucleic
R acid (RNA)
H H
R R
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

 Assign absolute configurations to each of the
asymmetric carbon atoms.
 How many stereoisomers are theoretically possible
for ribose?
Ribose

HOCH2 O R
OH a sugar unit in ribonucleic
R acid (RNA)
H H
R R
H Note: deoxyribose (from
DNA) is missing the 2-OH
HO OH

 Indicate the asymmetric carbons in ribose.

 Assign absolute configurations to each of the
asymmetric carbon atoms.
 How many stereoisomers are theoretically possible
for ribose? 4 asymmetric centers: 24 = 16.
 OH
O
H 2N
O O

Palytoxin OH

HO
OH OH
OH
OH
HO
OH
CH3
HO OH
OH OH
OH
OH
 from the Hawaiian coral “Limu-make-o-Hana”,
O
Palythoa toxica. OH
OH
 The most poisonous non-protein substance known.
 LD50 (mice) = 50 ng/kg i.p. HO
OH OH
O
 64 asymmetric centers! HO OH
O CH3 OH CH3 OH HO
OH OH
N O
H H OH
OH OH HO
HO N O H3C O OH HO
H
OH
O CH3 OH OH
H 3C O
CH3
OH OH
HO OH
OH
 OH
O
H 2N
O O

Palytoxin OH

HO
OH OH
OH
OH
HO
OH
CH3
HO OH
OH OH
OH
OH
 from the Hawaiian coral “Limu-make-o-Hana”,
O
Palythoa toxica. OH
OH
 The most poisonous non-protein substance known.
 LD50 (mice) = 50 ng/kg i.p. HO
OH OH
O
 64 asymmetric centers! HO OH
O CH3 OH CH3 OH HO
OH OH
N O
H H OH
OH OH HO
HO N O H3C O OH HO
H
OH
O CH3 OH OH
H 3C O
CH3
OH OH
HO OH
OH
 OH
O
H 2N
O O

Palytoxin OH

HO
OH OH
OH
OH
HO
OH
CH3
HO OH
OH OH
OH
OH
 from the Hawaiian coral “Limu-make-o-Hana”,
O
Palythoa toxica. OH
OH
 The most poisonous nonprotein substance known.
 LD50 (mice) = 50 ng/kg i.p. HO
OH OH
O
 64 asymmetric centers! HO OH
O CH3 OH CH3 OH HO
OH OH
N O
H H OH
OH OH HO
HO N O H3C O OH HO
H
OH
O CH3 OH OH
H 3C O
CH3
OH OH
HO OH
OH
 OH
O
H2N
O O

Palytoxin OH

HO
OH OH
OH
OH
HO
OH
CH3
HO OH
OH OH
OH
OH
 from the Hawaiian coral “Limu-make-o-Hana”,
O
Palythoa toxica. OH
OH
 The most poisonous nonprotein substance known.
 LD50 (mice) = 50 ng/kg i.p. HO
OH OH
O
 64 asymmetric centers! O CH3 OH
HO
CH3 OH
OH
HO
OH
OH
N O
H H OH
OH OH HO
HO N O H3C O OH HO
H
OH
O CH3 OH OH
H3C O
CH3
OH OH
HO OH
OH
Stereochemistry in Chemical Reactions
 Free radical bromination of butane:

H
C Br2
CH3 H C CH3
H h
CH2CH3 CH2CH3

Br CH2CH3
H CH3
C + C
H CH3
CH2CH3 Br
(S)-2-Bromobutane (R)-2-Bromobutane
Stereochemistry in Chemical Reactions
 Free radical bromination of butane:

H
C Br2
CH3 H C CH3
H h
CH2CH3 CH2CH3

Br CH2CH3
H CH3
C + C
H CH3
CH2CH3 Br
(S)-2-Bromobutane (R)-2-Bromobutane
Stereochemistry in Chemical Reactions
 Free radical bromination of butane:

H
C Br2
CH3 H C CH3
H h
CH2CH3 CH2CH3
a trigonal-planar intermediate
Br CH2CH3
H CH3
C + C
H CH3
CH2CH3 Br
(S)-2-Bromobutane (R)-2-Bromobutane
Stereochemistry in Chemical Reactions
 Free radical bromination of butane:

H
C Br2
CH3 H C CH3
H h
CH2CH3 CH2CH3
a trigonal-planar intermediate
Br CH2CH3
H CH3
C + C
H CH3
CH2CH3 Br
(S)-2-Bromobutane (R)-2-Bromobutane
Stereochemistry in Chemical Reactions
 Free radical bromination of butane:

H
C Br2
CH3 H C CH3
H h
CH2CH3 CH2CH3
a trigonal-planar intermediate
Br CH2CH3
H CH3
C + C
H CH3
CH2CH3 Br
(S)-2-Bromobutane (R)-2-Bromobutane

a racemic mixture
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
 Attack at C(2):
Br
Cl2 CH3
C Br C
H CH3 h CH2CH3
CH2CH3
(S)-2-Bromobutane

Br CH2CH3
Cl CH3
C + C
Cl CH3
CH2CH3 Br
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
 Attack at C(2):
Br
Cl2 CH3
C Br C
H CH3 h CH2CH3
CH2CH3
(S)-2-Bromobutane trigonal-planar intermediate
Br CH2CH3
Cl CH3
C + C
Cl CH3
CH2CH3 Br
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
 Attack at C(2):
Br
Cl2 CH3
C Br C
H CH3 h CH2CH3
CH2CH3
(S)-2-Bromobutane trigonal-planar intermediate
Br CH2CH3
Cl CH3
C + C
Cl CH3
CH2CH3 Br
a racemic mixture
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
BrAttackHat C(3):

Br
Cl2 H
C C C C
CH3 H h CH3 CH3
H CH3 H
2S
Br H Br Cl
CH3
C C + CH C C H
CH3 3
Cl
H H CH3
2S,3R 2S,3S
major minor
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
BrAttackHat C(3):

Br
Cl2 H
C C C C
CH3 H h CH3 CH3
H CH3 H
2S trigonal-planar intermediate
Br H Br Cl
CH3
C C + CH C C H
CH3 3
Cl
H H CH3
2S,3R 2S,3S
major minor
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
BrAttackHat C(3):

Br
Cl2 H
C C C C
CH3 H h CH3 CH3
H CH3 H
2S
Br H Br Cl
CH3
C C + CH C C H
CH3 3
Cl
H H CH3
2S,3R 2S,3S
major minor
a mixture of
diastereomers
Stereochemistry in Chemical Reactions
 Free radical chlorination of (S)-2-
bromobutane
BrAttackHat C(3):

Br
Cl2 H
C C C C
CH3 H h CH3 CH3
H CH3 H
2S
Br H Br Cl
CH3
C C + CH C C H
CH3 3
Cl
H H CH3
2S,3R 2S,3S
major minor
a mixture of
diastereomers
Resolution of Enantiomers
 Amphetamine
CH3 CH3 Synthetic
C + H C CH Ph
amphetamine is a
PhCH2 H
NH2 H2 N
2 racemic mixture.

CO2H
H C OH
HO C H
CO2H

CO2H CO2H
CH3 CH3
H C OH H C OH
C
H + H C
PhCH2 HO C H CH2Ph HO C H
NH3 H3N
CO2 CO2
Resolution of Enantiomers
 Amphetamine
CH3 CH3 Synthetic
C + H C CH Ph
amphetamine is a
PhCH2 H
NH2 H2 N
2 racemic mixture.

CO2H
H C OH
Add L-tartaric acid.
HO C H
CO2H

CO2H CO2H
CH3 CH3
H C OH H C OH
C
H + H C
PhCH2 HO C H CH2Ph HO C H
NH3 H3 N
CO2 CO2
Resolution of Enantiomers
 Amphetamine
CH3 CH3 Synthetic
C + H C CH Ph
amphetamine is a
PhCH2 H
NH2 H2 N
2 racemic mixture.

CO2H
H C OH
Add L-tartaric acid.
HO C H
CO2H

CO2H CO2H
CH3 CH3
H C OH H C OH
C
H + H C
PhCH2 HO C H CH2Ph HO C H
NH3 H3 N
CO2 CO2
Get a mixture of diastereomeric salts (crystalline).
Resolution of Enantiomers
 Amphetamine

Separate the diastereomers

by recrystallization.
CO2H
CH3 CH3
H C OH 10% H2SO4
H
C 2 H C SO 4
2-
CH2Ph HO C H CH2Ph
H3 N H3 N
CO2
Resolution of Enantiomers
 Amphetamine

Separate the diastereomers

by recrystallization.
CO2H
CH3 CH3
H C OH 10% H2SO4
H
C 2 H C SO 4
2-
CH2Ph HO C H CH2Ph
H3 N H3 N
CO2
Isolate the pure (+)
enantiomer as the sulfate salt.

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Education, Inc.