Direct enantioselective α-amination of amides guided by DFT prediction of E/Z selectivity in a sulfonium intermediate

Abstract

Chiral amines are a highly important class of compounds for which powerful synthetic approaches remain in high demand. Herein, we report an unprecedented method for the preparation of chiral α-amino amides from cheap and abundant starting materials. Our strategy relies on a direct amination of amides using enantiopure sulfinamides. It involves a [2,3]-sigmatropic rearrangement of a key sulfonium intermediate. We further show how quantum chemical calculations allow predictive insights into the critical E/Z selectivity of this amino-vinyloxy-sulfonium species.