Stereochemistry

1
Chapter 7
Stereochemistry
2
Stereochemistry Introduction
Constitutional isomers differing in constitution
different sequence and/or nature of bonds
Stereoisomers same sequence of bonds, but differ
in spatial array of groups
i. Conformation isomers differing by rotation or
partial rotation about single bonds butane
conformers, chair conformers of cyclohexane
rapidly interconvert at room temperature
ii. Configurational isomers individual isomers
are generally stable at room temperature -
cis- trans isomers e.g. cis- and
trans-1,2- dimethylcyclopropane - geometric
isomers e.g. (E)- and (Z)-2-butene -
enantiomers mirror image isomers which are
not superimposable (A-level)
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Stereogenic Centre
textbook definition p. 183 is ambiguous!
the centre which generates
stereochemistry
Stereogenic centre
A stereogenic centre is one at which a
hypothetical exchange of two atoms or groups
attached to an atom produces a different
stereoisomer (usually configurational isomer)!
stereogenic centre
stereogenic centre
4
Chiral Centre
Chiral centre chirogenic centre the centre
which generates chirality

• Chiral centre (asymmetric centre) is one
  which has four different atoms or groups attached

• Chiral centre is a subset of a stereogenic
  centre!

chiral (chirogenic) centre
A and B are . (. isomers)!
non-superimposable mirror images.

• an is chiral! a chiral compound is
  upon its mirror image.

Nomenclature of enantiomers use CIP system (same
as for nomenclature of (E)- and (Z)-isomers)
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Nomenclature of Enantiomers

• Priority a, b, c, d to groups by CIP-system
  reorientate structure with lowest priority group
  d pointing away

• Draw arrow from a ? b ? c
• Clockwise (R)- (Latin rectus to the
  right)
• Anticlockwise (S)- (Latin sinistro to the
  left dark!)

(S)-2-bromo- butane
(R)-2-bromo-butane

• Descriptors (R)- and (S)- designate absolute
  configuration
• of chiral centre - no relationship with sign of
  optical rotation

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Nomenclature of Enantiomers (cont.)

• Important to reorientate structure so that
  lowest priority group points away!

()-(1-bromoethyl) ethyl ether
(..)-2-butanol
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Nomenclature of Enantiomers (cont.)
Question

• Draw the structure for (S)-1-chloro-2-butanol
  indicating absolute configuration

Constitution ClCH2CH(OH)CH2CH3
Chiral centre (C) is at C2 groups attached
to C are HO- , ClCH2-, CH3CH2-, H- .
Priorities HO- a, ClCH2- b, CH3CH2- c, H-
d
(..)-
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Two Chiral Centres
Consider
(2R)
(3S)
(2.,3..)-2,3-dibromobutane
but .. is it chiral?
Compound C - two chiral centres.
is it non-superimposable upon its mirror image?

• mirror plane or plane of symmetry!

Consider C and its mirror image D
(2R)
(2S)
(3S)
(3R)
(2R,3S)- or ..-2,3-dibromobutane
C and D !
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Two Chiral Centres (cont.)
Meso compound (cont.) each chiral centre is
linked to the same types of substituents, which
reflect in the mirror plane
(2R,3S)- or meso-2,3-dihydroxybutanedioic
acid or meso-tartaric acid
(2R,3S)- or meso- 2,3-dibromobutane
m.p. 140 C
not a meso compound!
(1R,2S)-1,2-dibromo- cyclobutane
(2R,3S)-2-bromo-3-chlorobutane
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Diastereoisomers
Compounds C, E and F
(2R)
(2R)
(2S)
(3R)
(3S)
(3S)

• E,F not superimposable both chiral-
  enantiomers!

diastereoisomers!

• Relationship between C and E or C and F

• Stereoisomers which are not enantiomers are
  diastereoisomers or diastereomers.

m.p. 170 C
m.p. 140 C
(2R,3R )- 2,3-dihydroxybutanedioic
acid or (2R,3R)- tartaric acid
(2R,3S)- or meso- 2,3-dihydroxybutanedioic
acid or meso-tartaric acid
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Enantiomers and Diastereoisomers
Structural representations
Fischer Projections
(R)-Lactic Acid
(S)-Lactic Acid
S
R
R
S
R
S
(2R,3R)- ()- Tartaric Acid
meso- or (2R,3S)- Tartaric Acid
(2S,3S)- (-)- Tartaric Acid
meso compound number such that R-chiral centre
precedes S-chiral centre!
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Structural Representations (cont.)
Relationship between Fischer, Newman, sawhorse,
other projections
(2R,3R)- ()- Tartaric Acid
R
R
R
S
R
R
"flying wedge"
"zig-zag"
D-Glucose
'flying wedge' or 'zig-zag' projections used for
depicting stereostructures of reaction products
or natural products! not for examination!
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Properties of Enantiomers
Identical m.p., b.p., differ in specific
rotation Solution irradiated with plane
polarized light ? 589 nm (sodium D emission
line) in polarimeter. rotation ? ?? to the
right dextrorotatory d- or () to
the left levorotatory l or (-).
specific rotation ?589 ?.100/c.l
c conc. g./100mL l length of sample
tube (dm)

• Optically active compound displays optical
  rotation
• - pure enantiomer, or mixture of enantiomers
  containing more than 50 of one enantiomer.
• Racemic mixture mixture contains 50 of each
  enantiomer, ? 0.
• Racemate or racemic compound (rac)
  crystalline or pure liquid 11 mixture of
  enantiomers

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Properties of Enantiomers (cont.)
Examples
?D -12.4
?D 12.4
?D 0
m.p. 170 C
m.p. 140 C
m.p. 170 C
(2R,3S)- or meso- -tartaric acid
(2S,3S)-(-)- tartaric acid
(2R,3R)- ()-tartaric acid
Racemate
?D 0
rac- or (2RS,3RS)- tartaric acid or ()-
tartaric acid
m.p. 210 C

• crystals consist of 11
• mixture of enantiomers

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Stereochemistry Chemical Reactions

• In an achiral environment, if a reaction
  involving achiral or racemic reactants provides
  a chiral product, the product is obtained as a
  racemic mixture

2-Methyl-1-butene bromination
a. Ring opening of bromonium ion at less
substituted C atom
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Stereochemistry of Bromination (cont.)
b. Ring opening at more substituted carbon atom -
For both sets of reactions "a" and "b" energies
of transition state leading to top and bottom
bromonium ions exactly equal in energy ? equal
amounts of (R)- and (S)-products (enantiomers)
produced!
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Stereochemistry of Bromination (cont.)
(Z)-2-butene Ring opening of bromonium ion at
C-2
(2R,3R)-
(2S,3S)-
Stereochemistry of bromonium ion?
a meso compound - achiral!!
Configuration at C2 and C3 in products A and B?
A and B are enantiomers!
Opening at C3 of top bromonium ion ?
(2S,3S)-product B bottom ?
(2R,3R)-product A
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Stereochemistry of Bromination (cont.)
(E)-2-butene Ring opening of bromonium ion at
C-2
(2S,3R)-
(2R,3S)-
Stereochemistry of bromonium ions?
enantiomers!!
Configuration at C2 and C3 in products A and B?
A and B are meso compounds they are
identical!!
Opening at C3 of top bromonium ion ?
(2R,3S)-product B bottom ?
(2S,3R)-product A
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SN2 Reactions Stereochemistry
SN2 Inversion of configuration
Always for SN2 reactions. Note that (R)- and
(S)- descriptors may not always change depending
upon priority (a, b or c) of newly introduced
group ? problems
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SN1 Reactions Stereochemistry
SN1 For enantiomerically pure 3 alkyl halide
Carbocation planar and achiral in absence of
Br-, equal probability of addition of H2O from
top (retention) and bottom(inversion) to
give 50 (R)-, 50 (S)-products (complete
racemization).
However Br- associated with top face,
preference for H2O to add from bottom -
slightly more of (S)-2-phenyl-2-butanol is
obtained! (partial racemization)
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Stereochemistry and Nature

• In a chiral, non-racemic environment, a
  reaction may produce a chiral compound as a
  single enantiomer!

e.g. reactions catalysed by enzymes (chiral
non-racemic very large molecules) in Nature
(Section 7.9)
i. Perception of taste, metabolism of food, etc
Limonene
Asparagine
lemon odour
orange odour
bitter taste
sweet taste
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Stereochemistry and Nature (cont.)
2. Action of drugs in the body
Penicillamine
extremely toxic
anti-arthritic drug
ent-Morphine (unnatural)
Morphine
analgesic
no activity
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Stereochemistry and Nature (cont.)
Biosynthetic reactions in the body catalysed by
chiral enzymes
Cholesterol 8 chiral centres possibility of
256 stereoisomers only 1 biosynthesized in
body!
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Stereochemistry Problems
1. Give the stereostructure of the product
obtained when (R)-2- iodopentane is treated with
sodium acetate in acetone
(R)- 2-iodopentane CH3CH(I)CH2CH2CH3 chiral
centre (C) at C2 ? groups at C are I- , CH3-,
CH3CH2CH2, H- .
Priorities I- a, CH3CH2CH2- b, CH3- c, H-
d
(R)- 2-iodopentane
SN2 reaction with acetate inversion of
configuration
Stereostructure must be unambiguously indicated
(S)-2-pentyl acetate
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Stereochemistry Problems (cont.)

• Consider the following pairs of compounds. Are
  they i. constitutional
• isomers ii. enantiomers iii. identical
  compounds iv. diastereomers?

a.
Answer
each chiral (stereogenic) centre has same groups

• either they are enantiomers or they are identical

Easiest way is to exchange two groups at a
time! (remember definition of stereogenic centre
and hypothetical experiment)
Identical!
Enantiomer of i
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Stereochemistry Problems (cont.)

• (cont.) Consider the following pairs of
  compounds. Are they i.
• constitutional isomers ii. enantiomers iii.
  identical compounds iv. diastereomers?

b.
Answer
Solve as in previous question, or assign CIP
stereochemical descriptors (R)- or (S)- to each
chiral centre
(S)-
Identical!
(S)-
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Stereochemistry Problems (cont.)

• (cont.) Consider the following pairs of
  compounds. Are they i.
• constitutional isomers ii. enantiomers iii.
  identical compounds iv. diastereomers?

Answer
Note there are two chiral centres in each
molecule which have same groups attached.
?They are either diastereomers, or enantiomers
or identical (meso compound).
Molecules as drawn are mirror images assign (R)-
or (S)- to each chiral centre in i or ii.
As configuration is (1R,2S)-, ii is a meso
compound - possesses a mirror plane
Although ii is the mirror image of i, it is
superimposable on it
Compounds i and ii are identical
(1R,
2S)-
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Stereochemistry Problems (cont.)

• (cont.) Consider the following pairs of
  compounds. Are they i.
• constitutional isomers ii. enantiomers iii.
  identical compounds iv. diastereomers?

Answer
No chiral centres! . but ..
Are they mirror images?.............
Yes!
Are they superimposable? ........
No!
No plane of symmetry!......
They are enantiomers
There are many examples of chiral molecules which
do not possess a chiral centre