2.3.3.5 Baeyer-Villiger Reactions
Oxidation of ketones by peracids – the Baeyer-Villiger reaction [1349, 1350] – is a
reliable and useful method for preparing esters or lactones (Scheme 2.161). The
mechanism comprises a two-step process, in which the peracid attacks the carbonyl
group of the ketone to form the so-called tetrahedral ‘Criegee-intermediate’
[1351]. The fragmentation of this unstable species, which proceeds via expulsion
of a carboxylate ion going in hand with migration of a carbon–carbon bond, leads to
the formation of an ester or a lactone. The regiochemistry of oxygen insertion of the
R 1
S
R
2
R 1
S
R
2
O
R or S
Flavin-dependent
Monooxygenase
NAD(P)H
(recycling)
O 2
H 2 O
R
1
R
2
Enzyme* Config. Conv. [%] E.e. [%]
Me
c-Hexyl
CHMO
R
80
98
t-Bu
CH=CH 2
CHMO
R
78
98
Me
Ph
CHMO
R
88
99
Et
p-F-C 6 H 4
CHMO
S
96
93
CH 2 -CN
Ph
CHMO
R
90
92
CH 2 -CN
p-Me-C 6 H 4
CHMO
S
95
98
Me
c-Hexyl
HAPMO
S
>99
>99
Me
Ph
HAPMO
S
>97
>99
Me
2-Pyridyl
HAPMO
S
>99
>99
Me
4-Pyridyl
HAPMO
R
63
>99
* CHMO = Cyclohexanone monooxygenase, HAPMO = hydroxyacetone monooxygenase.
Scheme 2.160 Enzymatic oxidation of thioethers using isolated monooxygenases
2.3 Oxidation Reactions
189