Chemoenzymatic dynamic kinetic resolution of α-trifluoromethylated amines: influence of substitutions on the reversed stereoselectivity?

RSC Advances Pub Date: 2013-04-03 DOI: 10.1039/C3RA40526E

Abstract

Enzymatic resolution of α-trifluoromethylated amines via kinetic resolution (KR), dynamic kinetic resolution (DKR) employing CALB-Pd/Al2O3, and a one-pot sequential process of KR/DKR/KR was investigated comparatively for the first time. Although CALB-catalyzed KR of α-trifluoromethylated amines with substituents of methyl (1a), isopropyl (1c), phenyl (1d) and benzyl group (1e) can provide good stereoselectivity factors E from 31 to >200 respectively, DKR and sequential process of KR/DKR/KR possess better practical application potential because of the higher conversion (62%–84%) and the similar enantiomeric excesses (90%–99%). The enantiopreference and inversion for the α-trifluoromethylated amines displayed by CALB were observed and explained by docking modes. Namely, for 1,1,1-trifluoro-2-propylamine (1a), the product amide with R-configuration was obtained, and the enantiopreference was converted to S for the amines (1b–1e) with substituents larger than methyl group. The catalysts recycle, and scale-up experiments were demonstrated successfully. All these results indicated the high efficiency and green feature of this enzymatic process, and its application significance.

Graphical abstract: Chemoenzymatic dynamic kinetic resolution of α-trifluoromethylated amines: influence of substitutions on the reversed stereoselectivity
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