General

Organic Chemistry
Two credits
Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course,

by Robert C. Atkins and Francis A. Carey
Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

 Lecture 13

Chapter 7

Stereochemistry
 Fischer Projections

• Purpose of Fischer projections is to show

configuration at chirality center without
necessity of drawing wedges and dashes or
using models.

Dr. Wolf's CHM 201 & 202 7-3

 Rules
Rulesfor
forFischer
Fischerprojections
projections

Br Cl

Arrange the molecule so that horizontal

bonds at chirality center point toward you
and vertical bonds point away from you.
Dr. Wolf's CHM 201 & 202 7-4
 Rules
Rulesfor
forFischer
Fischerprojections
projections

Br Cl

F
Projection of molecule on page is a cross. When
represented this way it is understood that
horizontal bonds project outward, vertical bonds
are back.
Dr. Wolf's CHM 201 & 202 7-5
 Rules
Rulesfor
forFischer
Fischerprojections
projections

Br Cl

F
Projection of molecule on page is a cross. When
represented this way it is understood that
horizontal bonds project outward, vertical bonds
are back.
Dr. Wolf's CHM 201 & 202 7-6
 Physical Properties of
Enantiomers

Dr. Wolf's CHM 201 & 202 7-7

 Physical
Physicalproperties
propertiesofofenantiomers
enantiomers

Same:
melting point, boiling point, density, spectroscopy, etc..

Different:
properties that depend on shape of molecule
(biological-physiological properties) can be
different

Dr. Wolf's CHM 201 & 202 7-8

 Odor
Odor

CH3 CH3

O O

H3C CH2 H3C CH2

(–)-Carvone (+)-Carvone
spearmint oil caraway seed oil
S- configuration R- configuration
Dr. Wolf's CHM 201 & 202 7-9
 Chiral
Chiraldrugs
drugs

Ibuprofen is chiral, but normally sold as

a racemic mixture. The S enantiomer
is the one responsible for its analgesic
and antiinflammatory properties.

H
H3C
C CH2CH(CH3)2

C
HO
O
Dr. Wolf's CHM 201 & 202 7-10
 Reactions That Create A
Chiral Center

Dr. Wolf's CHM 201 & 202 7-11

 Many reactions convert achiral
reactants to chiral products.

It is important to recognize, however, that if all of the

components of the starting state (reactants, catalysts,
solvents, etc.) are achiral, any chiral product will be
formed as a racemic mixture.

This generalization can be more simply stated as

"Optically inactive starting materials can't give
optically active products." (Remember: In order for a
substance to be optically active, it must be chiral and one
enantiomer must be present in greater amounts than the
other.
 Example
Example

O
H
CH3COOH
CH3CH CH2 H3C C CH2
O

Achiral Chiral, but racemic

epoxidation from this direction
gives R epoxide

50% R

50%
S

epoxidation from this direction

gives S epoxide
 Example
Example

Br2, H2O
CH3CH CH2 CH3CHCH2Br

OH

Achiral Chiral, but racemic

 Example
Example

HBr
CH3CH CHCH3 CH3CHCH2CH3

Br

Achiral Chiral, but racemic

 Chiral Molecules
with
Two Chirality Centers

How many stereoisomers when

a particular molecule contains
two chiral centers?

Dr. Wolf's CHM 201 & 202 7-17

 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
What are all the possible R and S combinations of
the two chirality centers in this molecule?
 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
What are all the possible R and S combinations of
the two chirality centers in this molecule?

Carbon-2 R R S S
Carbon-3 R S R S
 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
4 Combinations = 4 Stereoisomers

Carbon-2 R R S S
Carbon-3 R S R S
 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
4 Combinations = 4 Stereoisomers

What is the relationship between these stereoisomers?

Carbon-2 R R S S
Carbon-3 R S R S
 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
enantiomers: 2R,3R and 2S,3S
2R,3S and 2S,3R

Carbon-2 R R S S
Carbon-3 R S R S
 2,3-Dihydroxybutanoic
2,3-Dihydroxybutanoicacid
acid

O
3 2
CH3CHCHCOH

HO OH
but not all relationships are enantiomeric
stereoisomers that are not enantiomers are:
diastereomers…….
similar but not identical chemical and physical properties

Carbon-2 R R S S
Carbon-3 R S R S
Fischer
FischerProjections
Projections

recall for Fischer CO2H

projection: horizontal
bonds point toward
you; vertical bonds
point away

staggered conformation
does not have correct CH3
orientation of bonds for
Fischer projection
Fischer
Fischerprojections
projections

transform
molecule to
eclipsed
conformation
in order to
construct
Fischer
projection
Fischer
Fischerprojections
projections

CO2H

H OH

H OH

CH3
 Erythro
Erythroand
andThreo
Threo

stereochemical prefixes used to specify relative

configuration in molecules with two chirality
centers

easiest to apply using Fischer projections

orientation: vertical carbon chain

 Erythro
Erythro

when carbon chain is vertical, same (or

analogous) substituents on same side of
Fischer projection
CO2H CO2H

H OH HO H

H OH HO H

–9.5° CH3 CH3 +9.5°

 Threo
Threo

when carbon chain is vertical, same (or

analogous) substituents on opposite sides of
Fischer projection
CO2H CO2H

H OH HO H

HO H H OH

+17.8° CH3 CH3 –17.8°

 Achiral Molecules
with
Two Chirality Centers

It is possible for a molecule to have

chirality centers yet be achiral.

Dr. Wolf's CHM 201 & 202 7-30

 2,3-Butanediol
2,3-Butanediol

2 3
CH3CHCHCH3

HO OH

Consider a molecule with two equivalently substituted

chirality centers such as 2,3 butanediol.
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

2R,3R 2S,3S 2R,3S

chiral chiral achiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

CH3 CH3 CH3

HO H H OH H OH

H OH HO H H OH

CH3 CH3 CH3

2R,3R 2S,3S 2R,3S

chiral chiral achiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

these two are

enantiomers

2R,3R 2S,3S
chiral chiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

CH3 CH3

HO H H OH
these two are
H OH HO H enantiomers

CH3 CH3

2R,3R 2S,3S
chiral chiral
Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

the third structure is

superposable on its
mirror image

2R,3S
achiral
Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

therefore, this structure

and its mirror image
are the same

it is called a meso form

a meso form is an achiral

molecule that has 2R,3S
chirality centers
achiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

CH3 therefore, this structure CH3

and its mirror image
HO H are the same H OH

HO H H OH
it is called a meso form
CH3 CH3
a meso form is an achiral
molecule that has 2R,3S
chirality centers
achiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

meso forms have a plane of

symmetry and/or a center of
symmetry

plane of symmetry is most

common case

top half of molecule is mirror

image of bottom half 2R,3S
achiral
 Three
Threestereoisomers
stereoisomersofof2,3-butanediol
2,3-butanediol

CH3 CH3
A line drawn
the center of
HO H H OH
the Fischer
projection of a
HO H H OH
meso form
bisects it into
CH3 CH3
two mirror-
image halves.
2R,3S
achiral
 Cholic
Cholicacid
acid
CH3
HO H
CH3 CH2CH2CO2H

H3C H

11 chirality centers
H H
211 = 2048 stereoisomers
HO OH one is "natural" cholic acid
H a second is the enantiomer of
natural cholic acid
2046 are diastereomers of cholic
acid
 How
Howmany
manystereoisomers?
stereoisomers?

maximum number of stereoisomers = 2n

where n = number of structural units capable of

stereochemical variation

structural units include chirality centers and cis

and/or trans double bonds

number is reduced to less than 2n if meso forms

are possible
 How
Howmany
manystereoisomers?
stereoisomers?

3-Penten-2-ol

E R E S

HO H H OH

Z R Z S

HO H H OH
 Stereoselective
Stereoselectivereaction
reaction
A single starting material can give two or more
stereoisomeric products, but gives one of them
in greater amounts than any other

H H H
CH3 H2 CH3 CH3
+
Pt CH3 H
CH2
H CH3

68% 32%
 Chirality Centers
Other Than Carbon
 Silicon
Silicon

b b
a a
Si d d Si

c c

Silicon, like carbon, forms four bonds in its stable

compounds and many chiral silicon compounds
have been resolved
 Nitrogen
Nitrogenininamines
amines

b b
a very fast a
N : : N

c c

Pyramidal geometry at nitrogen can

produce a chiral structure, but enantiomers
equilibrate too rapidly to be resolved
 Phosphorus
Phosphorusininphosphines
phosphines

b b
a slow a
P : : P

c c
Pyramidal geometry at phosphorus can produce a
chiral structure; pyramidal inversion slower than
for amines and compounds of the type shown have
been resolved