Catalytic Asymmetric Synthesis of 3‐Substituted Proline Derivatives by Using Phase‐Transfer‐Catalyzed Conjugate Addition

Abstract

AbstractThe catalytic enantio‐ and diastereoselective synthesis of trans‐3‐substituted proline derivatives has been accomplished by chiral phase‐transfer‐catalyzed asymmetric conjugate addition of N‐(diphenylmethylene)glycine ester to α,β‐unsaturated aldehydes. Various 3‐substituted prolines that contain aromatic, heteroaromatic, and alkyl groups were synthesized efficiently with good to high enantioselectivity. This synthetic method can be applied to the efficient enantioselective synthesis of core structures of L‐pyrrolysine and telaprevir, which are important biologically active compounds. The practicability of the method was demonstrated by a gram‐scale synthesis of a core structure of telaprevir.