Asymmetric reduction of 2-(N-arylimino)-3,3,3-trifluoropropanoic acid esters leading to enantiomerically enriched 3,3,3-trifluoroalanine

Enantiomerically enriched 3,3,3-trifluoroalanine (1) (up to 62 % ee) has been synthesized by the asymmetric reduction of 2-(N-arylimino)-3,3,3-trifluoropropanoic acid esters with a chiral oxazaborolidine catalyst and subsequent oxidative removal of N-aromatic moiety with retention of the configuration. Detailed optimization studies revealed that the effects of solvents, temperature, and the structural modification of the substrate were drastic on the enantioselectivity. The absolute configuration of 1 was determined to be (R) by X-Ray crystallographic analysis of the corresponding N-(S)-(+)-camphorsulfonyl derivative.