Page 19 - Demo-1

Examples of Racemization
The racemization/inversion step is key to a successful DKR. Following are a number of common techniques used for this step.
1) Acid or base catalyzed racemization
RR
O
2) Enzyme catalyzed racemization
Dehydrogenase OH (reversible)
CALB NEt3, R'OH
HN COOR' Ph O
up to 96% yield up to 98% ee
Redox-Enzyme (irreversible)
N
O
Ph
R1 R2
O
R1 R2
OH
R1 R2
NAD(P)+ NAD(P)H
Examples of Racemization (Cont'd)
3) Schiff base-mediated racemization
R1
CO2R
pyridoxal 5-phosphate
Alcalase R1
t-BuOH/H2O (19:1) H2N
90-98% ee, 87-95% yield
OH O
OH
H2N
CO2H
CO2R CO2R OPO
CHN CH2N ON
R1 R1 H+ pyridoxal 5-phosphate
4) Racemization via sp2 intermediates (redox, addition/elimination)
O High pH
RX
OH Lipase OAc RX Acyldonor RX
X = SR', OR', NHR', CN
X
H R1R2[M]HH X [M] + H X
R1 R2 [M]H R1 R2 H