Page 15 - Demo-1

Biocatalytic Dynamic Kinetic Resolution: Esterification via Ru-Catalyzed Racemization organometallic catalyst functions in tandem with enzyme
! Ru catalyzed racemization plus enzymatic esterification: DKR
Ph
Ph
Ph
Ph Ru H Ru Ph
OO H
OC CO CO CO
OH
2 mol% Ru catalyst P. cepacia lipase
4-Cl-C6H4OAc
cyclohexane, 60 °C
OAc
CO2Me
Ph
CO2Me
Ph
Ph
! Variation: One-pot aldol reaction — DKR. First DKR of !-hydroxy esters.
OO
Ph H Me OEt
i. LDA, THF ii. NH4Cl
iii. 6 mol% Ru catalyst P. cepacia lipase 4-Cl-C6H4OAc TBME, 60 °C, 6d
OAc O
OEt
catalyst
Backvall, Org. Lett., 2000, 2, 1037.
Substrate must have two differently sized groups adjacent to stereocenter These two groups cannot exceed the size of the active site in the enzyme
80% yield 98% ee
73% yield 95% ee
Backvall, Org. Lett., 2001, 3, 1209.
Biocatalytic Dynamic Kinetic Resolution: Ester Hydrolysis
! "-bromo esters racemized by Br—, resolved by enzymatic hydrolysis
Br
Ph
O
OMe
CH2P+Ph3Br—
Candida rugosa lipase H2O—MeOH
Ph
Br
O
OH
78% yield 79% ee
! Enantioenriched carboxylate product cannot racemize
H Br fast Br
Ph OMe Ph OMe
H Br
slow
Br
Ph O
O OOOO
Ph
Williams, Chem. Comm., 1998, 2519.