7'9 Reactions That Create A Chirality Center

1
7.9Reactions That Create A Chirality Center
2
Example

• Chiral, but racemic

Achiral
3
epoxidation from this direction gives R epoxide
R
4
Example
Br2, H2O
CH3CHCH2Br
OH

• Chiral, but racemic

Achiral
5
Example
HBr
CH3CHCH2CH3
Br

• Chiral, but racemic

Achiral
6
Many reactions convert chiral reactants to
chiral products.

• However, if the reactant is racemic, the product
  will be racemic also.
• Remember "Optically inactive starting
  materials can't give optically active products."

7
Example
HBr

• Chiral, but racemic

Chiral, but racemic
8
Example
HO2C
H
H2O
fumarase
CO2H
H
Fumaric acid
(S)-()-Malic acid
9
7.10Chiral MoleculeswithTwo Chirality Centers

• How many stereoisomers when a particular
  molecule contains two chirality centers?

10
Class Exercise
2
3

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

11
2,3-Dihydroxybutanoic acid
2
3

• 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
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2,3-Dihydroxybutanoic acid
2
3

• 4 Combinations 4 Stereoisomers

Carbon-2 R R S S Carbon-3 R S R S
13
2,3-Dihydroxybutanoic acid
2
3

• 4 Combinations 4 Stereoisomers
• What is the relationship between these
  stereoisomers?

Carbon-2 R R S S Carbon-3 R S R S
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2,3-Dihydroxybutanoic acid
2
3
enantiomers 2R,3R and 2S,3S 2R,3S and 2S,3R
Carbon-2 R R S S Carbon-3 R S R S
15



16
2,3-Dihydroxybutanoic acid
2
3
but not all relationships are enantiomeric

• stereoisomers that are not enantiomers are
  diastereomers

Carbon-2 R R S S Carbon-3 R S R S
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Isomers
constitutional isomers
stereoisomers
enantiomers
diastereomers
18
? -9.5
? 9.5
enantiomers
enantiomers
? -17.8
? 17.8



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Fischer Projections

• recall for Fischer projection horizontal bonds
  point toward you vertical bonds point away
• staggered conformation does not have correct
  orientation of bonds for Fischer projection

CO2H
CH3
20
Fischer projections

• transform molecule to eclipsed conformation in
  order to construct Fischer projection

21
Fischer projections
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Erythro and Threo

• stereochemical prefixes used to specify relative
  configuration in molecules with two chirality
  centers
• easiest to apply using Fischer projections
• orientation vertical carbon chain

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Erythro

• when carbon chain is vertical, same (or
  analogous) substituents on same side of Fischer
  projection

CO2H
H
HO
HO
H
CH3
9.5
9.5
24
Threo

• when carbon chain is vertical, same (or
  analogous) substituents on opposite sides of
  Fischer projection

17.8
17.8
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Two chirality centers in a ring
S
R
S
R
trans-1-Bromo-1-chlorocyclopropane

• nonsuperposable mirror images enantiomers

26
Two chirality centers in a ring
S
S
R
R
cis-1-Bromo-1-chlorocyclopropane

• nonsuperposable mirror images enantiomers

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Two chirality centers in a ring
S
S
R
R
cis-1-Bromo-1-chloro-cyclopropane
trans-1-Bromo-1-chloro-cyclopropane

• stereoisomers that are notenantiomers
  diastereomers

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7.11Achiral MoleculeswithTwo Chirality Centers

• It is possible for a molecule to have chirality
  centers yet be achiral.

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2,3-Butanediol
3
2

• Consider a molecule with two equivalently
  substituted chirality centers such as
  2,3-butanediol.

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Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
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Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
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Three stereoisomers of 2,3-butanediol
these two areenantiomers
2R,3R
2S,3S
chiral
chiral
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Three stereoisomers of 2,3-butanediol
these two areenantiomers
2R,3R
2S,3S
chiral
chiral
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Three stereoisomers of 2,3-butanediol
the third structure is superposable on
its mirror image
2R,3S
achiral
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Three stereoisomers of 2,3-butanediol

• therefore, this structure and its mirror
  imageare the same
• it is called a meso form
• a meso form is an achiral molecule that has
  chirality centers

2R,3S
achiral
36
Three stereoisomers of 2,3-butanediol
CH3

• 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
  chirality centers

H
HO
H
HO
CH3
2R,3S
achiral
37
Three stereoisomers of 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
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Three stereoisomers of 2,3-butanediol
A line drawnthe center ofthe Fischer
projection of ameso formbisects it intotwo
mirror-image halves.
2R,3S
achiral
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Cyclic compounds
meso
S
R
There are three stereoisomers of
1,2-dichloro-cyclopropane the achiral (meso)
cis isomer and two enantiomers of the trans
isomer.
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7.12MoleculeswithMultiple Chirality Centers
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How many 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

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Example

• 4 chirality centers
• 16 stereoisomers

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Cholic acid (Figure 7.12)

• 11 chirality centers
• 211 2048 stereoisomers
• one is "natural" cholic acid
• a second is the enantiomer of natural cholic acid
• 2046 are diastereomers of cholic acid

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How many 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

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How many stereoisomers?

• 3-Penten-2-ol

R
E
E
S
H
OH
HO
H
R
Z
Z
S
OH
H
H
HO