Reactions That Create A Chirality Center

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Reactions That Create A Chirality Center
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Many reactions convert achiral reactants to
chiral products.

• If all of the components of the starting
  materials (reactants, catalysts, solvents, etc.)
  are achiral, any chiral product will be formed as
  a racemic mixture.
• "Optically inactive starting materials can't give
  optically active products."

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Example

• Chiral, but racemic

Achiral
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epoxidation from this direction gives R epoxide
R
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Many reactions convert chiral reactants to chiral
products.
HBr
SN2
Chiral

• Chiral

However, if the reactant is racemic, the product
will be racemic also.
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Many biochemical reactions convertan achiral
reactant to a singleenantiomer of a chiral
product

• Reactions in living systems are catalyzed by
  enzymes, which are enantiomerically active.
• The enzyme (catalyst) is part of the reacting
  system that generate a chiral product.
• They don't violate "Optically inactive starting
  materials can't give optically active products."

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Example
HO2C
H
H2O
fumarase
CO2H
H
Fumaric acid
(S)-()-Malic acid
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Chiral MoleculeswithTwo Chirality Centers

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

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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
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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
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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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? -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
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Fischer projections

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

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Fischer projections
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Erythro and Threo

• stereochemical prefixes used to specify relative
  configuration in molecules with two chirality
  centers (before absolute)
• easiest to apply using Fischer projections when
  the carbon chain is vertical

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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
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Threo

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

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Two chirality centers in a ring
S
R
S
R
trans-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-chlorocyclopropane

• nonsuperposable mirror images enantiomers

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

• stereoisomers that are notenantiomers
  diastereomers

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Achiral MoleculeswithTwo Chirality Centers
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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
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
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
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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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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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MoleculeswithMultiple 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

• 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?

• 3-Penten-2-ol