17.14 Stereoselective Addition to Carbonyl Groups

1
17.14Stereoselective Addition to Carbonyl Groups

• Nucleophilic addition to carbonyl groups
  sometimes leads to a mixture of stereoisomeric
  products.

2
Example
NaBH4
80
20
3
Steric Hindrance to Approach of Reagent
this methyl group hindersapproach of
nucleophilefrom top
preferred direction of approach is to less
hindered (bottom) face of carbonyl group
4
Biological reductions are highly stereoselective

• pyruvic acid Æ S-()-lactic acid

NADH
H
enzyme is lactate dehydrogenase
5
Figure 17.11
O

C
H3C
O
C
carbonylbinding site
NADH
O
Pyruvate is bound at the active site of the enzyme
6
Figure 17.11
O

C
H3C
O
C
carbonylbinding site
NAD
H
OH
where it is reduced to (S)-()-lactate.
7
17.15Oxidation of Aldehydes
OH
H2O
RCH
RCH
RCOH
OH

• in aqueous solution

8
Example
K2Cr2O7
H2SO4
H2O
(75)
9
Example
K2Cr2O7
H2SO4
H2O
(75)
via
10
17.16Baeyer-Villiger Oxidationof Ketones

• Oxidation of ketones with peroxy acidsgives
  esters by a novel rearrangement.

11
General


Ketone
Ester
12
Example
CHCl3
(67)

• Oxygen insertion occurs between carbonyl carbon
  and larger group.
• Methyl ketones give acetate esters.

13
Stereochemistry
CHCl3
(66)

• Reaction is stereospecific.
• Oxygen insertion occurs with retention
  ofconfiguration.

14
Mechanism


R"COH
15
Mechanism


R"COH
First step is nucleophilicaddition of peroxy
acidto the carbonyl group of the ketone.

16
Mechanism


R"COH
Second step is migrationof group R from
carbonto oxygen. The weak OO bond breaks in
thisstep.

17
Biological Baeyer-Villliger Oxidation
O2.cyclohexanonemonooxygenase, coenzymes
bacterialoxidation

• Certain bacteria use hydrocarbons as a source of
  carbon. Oxidation proceeds via ketones, which
  then undergo oxidation of the Baeyer-Villiger
  type.