Metal‐mediated gem‐Difluoroallylation of N‐Acylhydrazones: Highly Efficient Synthesis of α,α‐Difluorohomoallylic Amines

Abstract

AbstractIndium‐mediated gem‐difluoroallylation of aldehyde‐derived N‐acylhydrazones 1a–1q and 4a–4g with 3‐bromo‐3,3‐difluoropropene 2 afforded α,α‐difluorohomoallylic hydrazides 3a–3q and 5a–5g in high yields, respectively. Functional groups such as nitro, phenolic hydroxyl, benzyloxy and even C=C bonds of α,β‐unsaturated aldehydes were compatible under this mild and operationally simple gem‐difluoroallylic reaction condition. By means of substitution of Zn powder for indium, gem‐difluoroallylation of ketone‐derived N‐acylhydrazones 6a–6d also provided the corresponding α,α‐difluorohomoallylic hydrazides 7a–7d in medium yields. The N–N bond cleavage of the hydrazide 3a proceeded smoothly to give the corresponding primary gem‐difluorohomoallylic amine 8, which could be converted to gem‐difluoro‐δ‐substituted α,β‐unsaturated lactam 11 via acryloylation followed by ring closing metathesis (RCM) reaction.