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.