Organocatalytic route to the enantioselective synthesis of syn/anti-α-hydrazino-γ-fluoro alcohols

Abstract

A general organocatalytic method has been developed for the asymmetric synthesis of α-hydrazino-γ-fluoro alcohols, a precursor to syn/anti-1,3-fluoro amines. The strategy employs α-fluorination catalyzed by proline-derived catalyst, (S)-α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol trimethylsilyl ether followed by Horner−Wadsworth−Emmons (HWE) olefination of aldehydes, and proline-catalyzed α-amination as the key steps. The title compounds showed excellent diastereoselectivity (up to 99:1) and enantioselectivity (up to 99 %).