Enzyme-catalyzed kinetic resolution of N-Boc-trans-3-hydroxy-4-phenylpyrrolidine

The first enzyme-catalyzed kinetic resolution of tert-butyl-3-hydroxy-4-phenylpyrrolidine-1-carboxylate is presented. Enzyme, solvent and temperature optimization resulted in a new resolution method with E = 40 enantioselectivity. The acetate derivative of the (+)-(3S,4R) enantiomer formed while the (−)-(3R,4S) isomer remained intact. Very good enantioselectivities (E > 200) were achieved in the enzyme-catalyzed alcoholysis of the racemic acetate in i-propanol and t-butanol where the (+)-(3S,4R) enantiomer was prepared in pure form (ee > 99.7%). Absolute configuration of the (−)-(3R,4S)-enantiomer was determined by single crystal X-ray diffraction method.