Unfunctionalized, alpha-epimerizable nonracemic ketones and aldehydes can be accessed by crystallization-induced dynamic resolution of imines.
This paper describes an operationally simple deracemization process of aldehydes and ketones. This new crystallization-induced dynamic resolution (CIDR) protocol allows for nearly complete conversion of the racemic mixture into one enantiomer. Crystallization of imines derived from racemic ketones or aldehydes 1 and trans-(1R,2R)-1-amino-6-nitroindan-2-ol (2) afforded diastereomerically pure, crystalline imines 3. Biphasic hydrolysis of 3 then affords recovered 2 and enantiomerically enriched 1 in high yield and er (substrate, yield/ee: 2-methylcyclohexanone, 97%/92; 2-ethylhexanal, 94%/98; 2-methylcyclopentanone, 94%/98; 2-cyclohexylcyclohexanone, ND/98; 3-methyl-2-pentanone, ND/76). The scope, limitations, and industrial perspective of this process are discussed. This highly effective CIDR process is likely due to pi-stacking of 2 and a hydrogen bonding of the imine with the free hydroxyl of 2 in the solid state.
Kosmrlj
Janez
J
Chemical Process R&D, Lilly Research Laboratories, Indianapolis, IN 46285-4813, USA. janez.kosmrlj@uni-lj.si
Weigel
Leland O
LO
Evans
David A
DA
Downey
C Wade
CW
Wu
Jimmy
J