Carey Chapter 7 Stereochemistry

1
7.7 Fischer Projections

• Purpose of Fischer projections is to show
  configuration at chirality center without
  necessity of drawing wedges and dashes or using
  models.

2
Rules for Fischer projections
H
Cl
Br
F

• Arrange the molecule so that horizontal bonds at
  chirality center point toward you and vertical
  bonds point away from you.

3
Rules for Fischer projections
H
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.

4
Rules for Fischer projections
H
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.

5
7.8Physical Properties of Enantiomers
6
Physical properties of enantiomers

• Same melting point, boiling point, density,
  etc
• Different properties that depend on shape of
  molecule (biological-physiological properties)
  can be different

7
Odor
CH3
CH3
O
O
H3C
H3C
CH2
CH2
()-Carvonespearmint oil
()-Carvonecaraway seed oil
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Chiral drugs

• Ibuprofen is chiral, but normally sold asa
  racemic mixture. The S enantiomer is the one
  responsible for its analgesic and
  antiinflammatory properties.

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7.9Reactions That Create A Chiral Center
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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.

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Example

• Chiral, but racemic

Achiral
12
epoxidation from this direction gives R epoxide
R
13
epoxidation from this direction gives R epoxide
R
S
epoxidation from this direction gives S epoxide
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epoxidation from this direction gives R epoxide
50
R
50
S
epoxidation from this direction gives S epoxide
15
Example
Br2, H2O
CH3CHCH2Br
OH

• Chiral, but racemic

Achiral
16
Example
HBr
CH3CHCH2CH3
Br

• Chiral, but racemic

Achiral
17
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."

18
Example
HBr

• Chiral, but racemic

Chiral, but racemic
19
Many biochemical reactions convertan achiral
reactant to a singleenantiomer of a chiral
product

• Reactions in living systems are catalyzed by
  enzymes, which are enantiomerically homogeneous.
• The enzyme (catalyst) is part of the reacting
  system, so such reactions don't violate the
  generalization that "Optically inactive starting
  materials can't give optically active products."

20
Example
HO2C
H
H2O
fumarase
CO2H
H
Fumaric acid
(S)-()-Malic acid
Achiral
Single enantiomer
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7.10Chiral MoleculeswithTwo Chirality Centers

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

22
2,3-Dihydroxybutanoic acid
2
3

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

23
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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a -9.5
a 9.5
enantiomers
enantiomers
a -17.8
a 17.8



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2,3-Dihydroxybutanoic acid
2
3
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
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Isomers
constitutional isomers
stereoisomers
enantiomers
diastereomers
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a -9.5
a 9.5
enantiomers
diastereomers
enantiomers
a -17.8
a 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
32
Fischer projections

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

33
Fischer projections
34
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

35
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
36
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-2-chlorocyclopropane

• nonsuperposable mirror images enantiomers

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Two chirality centers in a ring
S
S
R
R
cis-1-Bromo-2-chlorocyclopropane

• nonsuperposable mirror images enantiomers

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Two chirality centers in a ring
S
S
R
R
cis-1-Bromo-2-chloro-cyclopropane
trans-1-Bromo-2-chloro-cyclopropane

• stereoisomers that are not enantiomers
  diastereomers

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7.11Achiral MoleculeswithTwo Chirality Centers

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

41
2,3-Butanediol
3
2

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

42
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
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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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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.