Page 243 - Cascade_Biocatalysis_Integrating_Stereoselective_and_Environmentally_Friendly_Reactions

9.2 Enzyme-Catalyzed Stereoselective Reactions in Continuous-Flow Systems 219

OH OCOMe OH
MeCO-X
R R′ Solvent Lipase R R′ + R R′
rac-23a–r 24a–r 23a–r

OCOMe OCOMe OCOMe
O
n OCOMe
(R)-24a (n = 1) (R)-24f
(R)-24b (n = 3)
(R)-24g (R)-24h
(R)-24c (n = 4)
(R)-24d (n = 5)
(R)-24e (n = 7)
OCOMe OCOMe OCOMe OCOMe
MeOCO Br
S
(R)-24i (R)-24j (R,R)-24k (R,R)-24I

OCOMe N OCOMe OCOMe
N OCOMe
N N
O
O
(R,R)-24m (R,R)-24n (R)-24o (S)-24p

OCOMe
OCOMe
BnO OH
N
N
BnO OBn
OH
L-(−)-24q (R)-24r

Figure 9.9 Hydrolase-catalyzed kinetic resolution of secondary alcohols 23a–r by acylation
in continuous-flow PBRs and structure of the products 24a–r.

Vinyl acetate served most often as acylating agent but ethyl acetate in toluene [120]
or vinyl propionate in supercritical carbon dioxide (scCO ) [132] or vinyl laurate in
2
scCO [123] were also used.
2
Interesting reactor setups were tried with the KR of rac-23i. For example, a
silica monolith PBR was prepared by entrapment of Burkholderia cepacia lipase
in silicates formed from n-butyl-substituted precursors [121]. Higher rates of
acylation and increased enantioselectivity were found, as compared to the reaction
with nonimmobilized lipase in batch mode and a conversion of 40% and ee >98%