17.14
Stereoselective Addition to
Carbonyl Groups
Nucleophilic addition to carbonyl
groups sometimes leads to a mixture
of stereoisomeric products.
H3C
Example
CH3
O
H3C
CH3
H3C
CH3
NaBH4
OH
H
OH
H
80%
20%
Steric Hindrance to Approach of Reagent
this methyl group hinders
approach of nucleophile
from top
–
H3B—H
preferred direction of
approach is to less hindered
(bottom) face of carbonyl group
Biological reductions are highly stereoselective
pyruvic acid  S-(+)-lactic acid
CO2H
O
CH3CCO2H
NADH
HO
H
H+
CH3
enzyme is lactate dehydrogenase
Figure 17.11
O
H3C
NAD–H
C
carboxylat
e
C–
O binding site
O
carbonyl
binding site
Pyruvate is bound at the active site of the enzyme
Figure 17.11
O
H3C
NAD+
H
C
carboxylat
e
C–
O binding site
OH
carbonyl
binding site
where it is reduced to (S)-(+)-lactate.
17.15
Oxidation of Aldehydes
OH
O
RCH
H2O
RCH
O
RCOH
OH
in aqueous solution
Example
O
O
CH
O
K2Cr2O7
H2SO4
H2O
O
COH
(75%)
Example
O
O
O
K2Cr2O7
CH
H2SO4
H2O
O
COH
(75%)
OH
via
O
CH
OH
17.16
Baeyer-Villiger Oxidation
of Ketones
Oxidation of ketones with peroxy acids
gives esters by a novel rearrangement.
General
O
O
RCR' + R"COOH
Ketone
O
O
ROCR' + R"COH
Ester
Example
O
O
CCH3
O
C6H5COOH
CHCl3
OCCH3
(67%)
Oxygen insertion occurs between carbonyl
carbon and larger group.
Methyl ketones give acetate esters.
Stereochemistry
O
O
O
CCH3
H3C
H
H
C6H5COOH
CHCl3
OCCH3
H3C
H
H
(66%)
Reaction is stereospecific.
Oxygen insertion occurs with retention of
configuration.
Mechanism
O
O
RCR' + R"COOH
O
O
ROCR' + R"COH
Mechanism
O
O
O
RCR' + R"COOH
First step is nucleophilic R
addition of peroxy acid
to the carbonyl group of
the ketone.
O
ROCR' + R"COH
O
H
C
R'
O
OCR"
O
Mechanism
O
O
O
RCR' + R"COOH
Second step is migration R
of group R from carbon
to oxygen. The weak
O—O bond breaks in this
step.
O
ROCR' + R"COH
O
H
C
R'
O
OCR"
O
Biological Baeyer-Villliger Oxidation
bacterial
oxidation
O
O 2.
cyclohexanone
monooxygenase,
coenzymes
O
Certain bacteria use hydrocarbons as a
source of carbon. Oxidation proceeds via
ketones, which then undergo oxidation of the
Baeyer-Villiger type.
O