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Unit 3 Stereochemistry

Stereoisomers
Chirality
(R) and (S) Nomenclature
Depicting Asymmetric Carbons
Diastereomers
Fischer Projections
Stereochemical Relationships
Optical Activity
Resolution of Enantiomers

Stereochemistry
Stereochemistry:
The study of the three-dimensional

structure of molecules

Structural (constitutional) isomers:


same molecular formula but different

bonding sequence

Stereoisomers:
same molecular formula, same bonding

sequence, different spatial orientation

Stereochemistry

CH3
O

Stereochemistry plays an important role in

determining the properties and reactions of


H
organic compounds:
H3C

CH3

CH3
O

H3C

CH2

H
CH2

Caraway seed

O
H
H2C

CH3

spearmint

Stereochemistry
The properties of many drugs depends on their

stereochemistry:
HN

O
O
CH
CH3
NH3NH

O
NHCH3

Cl

HN

Cl

Cl

O
CH3NH

Cl

(S)-ketamine

(R)-ketamine

anesthetic

hallucinogen

Stereochemistry
Enzymes are

capable of
distinguishing
between
stereoisomers:

Types of Stereoisomers
Two types of stereoisomers:
enantiomers
two compounds that are nonsuperimposable

mirror images of each other

diastereomers
Two stereoisomers that are not mirror

images of each other

Geometric isomers (cis-trans isomers) are

one type of diastereomer.

Chiral
Enantiomers are chiral:
Chiral:
Not superimposable on its mirror image
Many natural and man-made objects are chiral:
hands
scissors
screws (left-handed vs. right-handed threads)
Right hand threads
slope up to the right.

Chiral
Some molecules are chiral:

Asymmetric
(chiral) carbon

Asymmetric Carbons
The most common feature that leads to

chirality in organic compounds is the presence


of an asymmetric (or chiral) carbon atom.
A carbon atom that is bonded to four
different groups

In general:
no asymmetric C
1 asymmetric C
> 2 asymmetric C

usually achiral
always chiral
may or may not be
chiral

Asymmetric Carbons
Example: Identify all asymmetric carbons
present in the following compounds.

Br

OH H

H3C

CH3

CH2CH3
H
H

Br

Br
Br

H CH
3

Achiral
Many molecules and objects are achiral:
identical to its mirror image
not chiral

Cl Cl

Cl Cl

Internal Plane of Symmetry


Cis-1,2-dichlorocyclopentane contains two

asymmetric carbons but is achiral.


contains an internal mirror plane of
symmetry
s
H

Cl

Cl

Any molecule that has an internal mirror plane

of symmetry is achiral even if it contains


asymmetric carbon atoms.

Internal Plane of Symmetry


Cis-1,2-dichlorocyclopentane is a meso

compound:
an achiral compound that contains chiral
centers
often contains an internal mirror plane of
symmetry

Internal Plane of Symmetry


Example: Which of the following compounds contain
an internal mirror plane of symmetry?
HO2C
HO
H

HO2C
HO
H

CO2H
OH
H

H Br

CH2CH3
C

H3CH2C

CO2H
H
OH

HO

H
Br

O
C OHF
C H

CH3
H

H3C

H
C
F

Cl
H

Chiral vs. Achiral


To determine if a compound is chiral:
0 asymmetric carbons:
Usually achiral
1 asymmetric carbon:
Always chiral
2 asymmetric carbons:
Chiral or achiral
Does the compound have an internal plane

of symmetry?
Yes:
achiral
No:
If mirror image is nonsuperimposable, then its chiral.
If mirror image is superimposable,
then its achiral.

Conformationally Mobile Systems


Alkanes and cycloalkanes are conformationally

mobile.
rapidly converting from one conformation to
another

In order to determine whether a cycloalkane is

chiral, draw its most symmetrical conformation


(a flat ring).

Chiral vs. Achiral

Br

Br

CHthe
3
Example: Identify
following molecules as
chiral or achiral.
CH3 C CH2CH3
Cl
CH3CHCH2CH2CH3

CH3

Br

Br

Cl

CH3

CH3CH2

CH3CCH2CH3
Cl

Br
H

Br
H

trans-1,3-dibromocyclohexane
CH2CHethylcyclohexane
3

H
Br

H
C

Br

CH2CH3

(R) And (S) Nomenclature


Stereoisomers are different compounds and

often have different properties.

Each stereoisomer must have a unique name.


The Cahn-Ingold-Prelog convention is used to

identify the configuration of each asymmetric


carbon atom present in a stereoisomer.
(R) and (S) configuration

(R) and (S) Nomenclature


The two enantiomers of alanine are:

CO2H

CO2H
C
H3C

H
NH2

Natural alanine
(S)-alanine

H
H2N

C
CH3

Unnatural alanine
(R)-alanine

(R) and (S) Nomenclature


Assign a numerical priority to each group

bonded to the asymmetric carbon:


group 1 = highest priority
group 4 = lowest priority

Rules for assigning priorities:


Compare the first atom in each group (i.e.

the atom directly bonded to the asymmetric


carbon)
Atoms with higher atomic numbers have
higher priority

(R) and (S) Nomenclature


Cl 1
3

C 2
H3 C
OCH2CH3
H
4

CH3

C H4
NH2
1 F
2

Example priorities:
I > Br > Cl > S > F > O > N >
1H

13C

>

12C

> 3H > 2H >

(R) and (S) Nomenclature


In case of ties, use the next atoms along the

chain as tiebreakers.

2 CH CH Br
2
2

C
3 CH CH
2
3

H4
CH(CH3)2
1

CH(CH3)2 > CH2CH2Br > CH3CH2

C Y
(R) and (S)
Nomenclature
C Y
Y

Y
Treat double and
triple bonds as if both atoms
C Y
Y
or triplicated:
O in the bondC were
C
C Yduplicated

C
C

OH
C Y
CH2OH

C
Y

O 2 H
Y C

1
C C OH
4 H CH2OH
3

Y
Y
C

Y
C

C O
Y
C Y2
O C H
C
C 4 HY
C
Y C

OH
CH2OH
Y3

Y
Y
C
C
Y

C
Y

(R) and (S) Nomenclature


Using a 3-D drawing or model, put the 4th

priority group in back.

Look at the molecule along the bond between

the asymmetric carbon and the 4th priority


group.

Draw an arrow from the 1st priority group to

the 2nd group to the 3rd group.


Clockwise arrow
Counterclockwise arrow

(R) configuration
(S) configuration

(R) and (S) Nomenclature

CH3)2

Example: Identify the asymmetric carbon(s) in


each of the following compounds and determine
whether it has the (R) or (S)Oconfiguration.

CH3

CH3
C
CH2C
CH3
CH2CH3
OHH
OH

H3

Br
C

CH3
H

C
CH3 Br

CO2H

CH(CH3)2
Br

CH3

COH
CH2C
H OH

(R) and (S) Nomenclature


Example: Name the following compounds.

CH2CH3
Br
H

CH3

Br

CH3

CH3

(R) and (S) Nomenclature


When naming compounds containing multiple

chiral atoms, you must give the configuration


around each chiral atom:
position number and configuration of each
chiral atom in numerical order, separated by
commas, all in ( ) at the start of the
compound name

H Br
H3C

H
Cl
CH3

(2S, 3S)-2-bromo-3-chlorobutane

Depicting Structures with Asymmetric


Carbons
Example: Draw a 3-dimensional formula for (R)2-chloropentane.
Step 1: Identify the asymmetric carbon.

Cl
CH3 C* CH2CH2CH3
H
Step 2: Assign priorities to each group attached to
the asymmetric carbon.
1

Cl

3 CH C
3

H 4

2
CH2CH2CH3

Depicting Structures
with Asymmetric
Cl
Carbons
CH3 C

CH2CH2CH3

Step 3: Draw a skeleton with the asymmetric carbon


in the center and H
the lowest priority group attached to
the dashed wedge (i.e. pointing away from you).

Cl
CH3 C

C
CH
H 2CH2CH3

Step 4: Place the highest priority group at the top.

Cl
H

Depicting Structures with Asymmetric


Cl
Carbons
CH3
CH5:
CForCH
Step
(R)2CH
configuration,
place the 2nd and
2
3
3rd priority groups around the asymmetric
H
carbon in a clockwise direction.
Cl
H

C
CH3 CH2CH2CH3

Step 6: Double-check your structure to make


sure that it has the right groups and the right
configuration.

Depicting Structures with Asymmetric


Carbons
Example: The R-enantiomer of ibuprofen is not
biologically active but is rapidly converted to the
active (S) enantiomer by the body. Draw the
structure of the R-enantiomer.

HO2CCH
CH3

CH2CH(CH3)2

Depicting Structures with Asymmetric


Carbons
Example: Captopril, used to treat high blood
pressure, has two asymmetric carbons, both with
the S configuration. Draw its structure.

O
N
CO2H

CHCH2SH
CH3