Stereochemistry

1
Chapter 9

• Stereochemistry

2
Chapter 9

• Enantiomers
• Diastereomers
• Reactions involving enantiomers.

3
Types of Isomers
4
Molecular Model
5
mirror image
6
mirror image
molecule
Molecule is chiral if molecule and its mirror
image are NOT superimposable.
Whether molecule and its mirror image are
superimposable or not superimposable depends on
the attached groups.
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mirror image
molecule
When the groups are different, the molecule
and its mirror image are NOT superimposable.
The molecule is said to be chiral.
8
Molecule 2
Molecule 1
When two molecules are mirror images and
NOT superimposable, they are called enantiomers.
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molecule
The above molecule has a plane of symmetry.
When a plane of symmetry exist, the molecule is
achiral.
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molecule
When four groups are different, a plane of
symmetry does not exist and therefore the
molecule is chiral.
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molecule
Chiral center is indicated by an .
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Cl
Methylene chloride
C
Cl
H
H
A plane (formed by Cl - Cl - C) of symmetry exist.
The molecule and its mirror image are
superimposable.
Methylene chloride is achiral.
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F
Cl
C
I
H
No plane of symmetry exist.
The molecule and its mirror image are not
superimposable.
The molecule is chiral.
C is the asymmetric carbon.
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achiral chiral
achiral
achiral
chiral
chiral


A
B
Are A and B different?
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A
B
A and B are enantiomers (because they are mirror
images but not superimposable).
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Lactic acid
Lactic acid
A new naming system is needed.
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Polarimetry
Lactic acid is chiral or optically active.
Lactic acid is d or .
Dextrorotatory d() and levorotatory l(-)
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From polarimetry results ...
(l or -) - Lactic acid
(d or ) - Lactic acid
19
Place at all chirality centers. Indicate
whether the compound is optically active. If it
is, assign d or l.
Menthol
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Answer Key




Menthol
Coniine
Toluene
(active)
(inactive)
(active)


Phenobarbital
Camphor
(inactive)
(active)
d or l can only be assigned after doing the
experiment.
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R, S Assignment
1
4
2
3
S
22
R, S Assignment
Clockwise - R Anti-clockwise - S
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R, S d, l
R, S - from molecular geometry (absolute
configuration).
d(), l(-) - from experiment (polarimetry).
R, S, and d, l - no relationship (see Fig 9.8, p
317).
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Assign R or S to the chirality center ...
25
Answer Key
R
S
S
26
Draw a tetrahedral representation of
(S)-2-pentanol
27
Answer Key
28
Chapter 9

• Enantiomers
• Diastereomers
• Reactions involving enantiomers.

29
Types of Isomers
30
Diastereomers - cis trans
Not mirror images of each other.
Enantiomers
Achiral
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Types of Isomers
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Diastereomers - configurational(two or more
chiral carbons)
1
S

2
R
3

4
33
Diastereomers - configurational(two or more
chiral carbons)
1
2R
2S

2
3R
3
3S

4
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R,S Permutations
2R
2S
3R
3S
2R
2R,3R
2R,3S
2n rule
2S
2S,3R
2S,3S
3R
3S
Red - Red - enantiomers
Green - Green - enantiomers
Red - Green - diastereomers
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2R,3R
2R,3S
2S,3R
2S,3S
enantiomers
enantiomers
diastereomers
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meso
2n rule fails
2n rule works
37
2-bromo-3-chlorobutane
2n 4


(2S,3S)
(2R,3S)
(2S,3R)
(2R,3R)
2-bromo-3-chlorobutane has only 3 stereoisomers,
not 4! The meso is achiral.
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Types of Isomers
39
Assign R, S to each chiral centers. Which are
enantiomers, and which are diastereomers?
40
Answer Key
4
R
S
3
R
S
R
R
2
S
S
1
(2R,3R)
(2R,3S)
(2S,3R)
(2S,3S)
(2R,3S) and (2S,3R) are mirror images, therefore
they are enantiomers.
(2R,3R) and (2S,3S) are mirror images, therefore
they are enantiomers.
(2R,3S) and (2S,3R) are diastereomers with
(2R,3R) and (2S,3S).
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Which of the following structures represent meso
compounds?
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Answer Key
meso
meso
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Fischer Projection
A
A

B
D
B
D
C
C
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Allowed Fischer Rotations
C
B
D
A
180o
A
B
D
B
Holding D
(A, B, or C)
C
C
A
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Fischer Projection
determine if two structures represent the same or
different enantiomers.
46
Which of the following Fischer projections
represent the same enantiomer?
A
B
C
D
47
Answer Key
A B
C D
enantiomeric
48
Assign R or S to the following molecules.
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Answer Key
S
R
S
50
R, S, , -
R (-) Lactic acid
S (-) Glyceraldehyde
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Absolute configuration

• R or S configuration leads to 3-D representation
  - absolute configuration.
• X-ray crystallography (since 1951) yields the
  configuration of the chiral molecule.
• Polarimetric measurement determines the () or
  (-) of the same molecule.
• Thus R or S and or - can be assigned.

52
Chapter 9

• Enantiomers
• Diastereomers
• Reactions involving enantiomers.

53



(-) - 2 - butanol
() - 2 - butanol
Change in plane polarized light.
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-

R
S
Inversion has occurred at the chiral carbon -
Walden Inversion (1893).
Start with an optically active compound end with
an optically active compound.
SN2 reaction.
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?
SN1
a
-
Racemic mixture
b
achiral planar


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a
-
b


If racemic mixture is 50-50, path a and b
have equal probability to occur - complete
racemization - optically inactive.
If racemic mixture is not 50-50 (e.g., the
leaving group, Br-, hinders the attacking
nucleophile, CH3CH2OH) - partial racemization -
still optically active.
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Absolute Configuration
S
a
R
-
b
R

Rotated plane polarized light

No Rotation reference line
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Stereochemistry ? Mechanism
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Chapter 9

• Enantiomers
• Diastereomers
• Reactions involving enantiomers.