Deoxygenative Amination of Unactivated Primary Alcohols Using Sulfonimidoyl Fluorides as an Ammonia Surrogate

Abstract

Herein, we describe a novel strategy for the highly selective amination of inactivated primary alcohols with bench-stable, readily available N-Boc-benzenesulfonimidoyl fluoride as a new ammonia surrogate, providing easy access to amines bearing easily removable N-Boc and N-benzenesulfonyl groups. The deoxygenative amination involves a key sulfonimidate ester intermediate generated via a sulfur(VI) fluoride exchange (SuFEx) click reaction, which subsequently undergoes an unprecedented [1,3] O-to-N rearrangement. The reaction displays high tolerance toward a wide array of functional groups, which are typically sensitive to the previously reported aminations of alcohols to primary amines, and features broad substrate scope, mild reaction conditions, and excellent selectivity for primary alcohols. Moreover, our methodology can be applied to the efficient and gram-scale synthesis of dopamine D3 receptor antagonists NGB 2904 and BP897.