latter problem was circumvented by adding silica gel to the mixture, which catalyzed the reversible dissociation of the thioacetal into thiol and aldehyde. With the
latter modification, a range of (S)-hemithioacetal esters were obtained in excellent
optical purities with yields being considerably beyond the usual 50% limitation for
classical kinetic resolutions.
• Stereochemically stable sec-alcohols can be racemized via an oxidationreduction sequence catalyzed by (transition) metal complexes based on Al, Ru,
Rh, and Ir [239, 240]. More labile allylic alcohols could be racemized using a
vanadium-catalyst [241]. However, both racemization techniques have their
OH
C≡N
R
OAc
C≡N
R
OH
C≡N
R
Pseudomonas sp.
lipase
+
rac
vinyl acetate
organic solvent
R
Solvent
e.e. [%] of
Selectivity
Acetate
Cyanohydrin
(E)
n-Pr
CH 2 Cl 2
5 5
3 3
5
Ph-CH 2 -O-CH 2 -
none
55
95
12
PhCH 2 Cl 2
6 8
8 0
1 3
4-HO-C 6 H 4 -
C H 2 Cl 2
7 9
5 0
1 4
Ph-(CH 2 ) 2 -
C H 2 Cl 2
95
86
100
C≡N
HO
O
H
R
OAc
C≡N
R
OH
C≡N
R
in-situ
racemization
anion exchange
resin
Pseudomonas sp.
lipase
i-propenyl acetate
e.e. 47-91%
R = aryl, heteroaryl, alkyl
rac
sole product
S
i-Pr 2 O
Scheme 3.15 Kinetic and dynamic resolution of cyanohydrins
O
H
R 1
R
2
OAc
S
R 1
R
2
OH
S
R 1
silica gel (cat.)
in-situ
racemization
rac
vinyl acetate
Pseudomonas sp.
lipase
t-BuOMe
+
HS-R 2
S
R 1
R 2
Product
yield [%]
e.e. [%]
-CO 2 Me
n-Bu63
>95
-CO 2 Me
Et 3 Si-O-(CH 2 ) 2 -
87
90
Ac-O-CH 2 -
n-Bu87
87
Ac-O-CH 2 -
i-Pr65
>95
Ac-O-CH 2 -
n-Octyl85
>95
Scheme 3.16 Dynamic resolution of hemithioacetals
3.1 Enzymes in Organic Solvents
339