An Investigation into the Sulfonamide Scope of Intermolecular Anti-Markovnikov Hydroamination Enabled by Oxidative Proton-Coupled Electron Transfer

Abstract

Most of the current approaches to olefin hydroamination for N-alkyl amide generation involve transition-metal cross-coupling reactions, which typically provide solely Markovnikov regioselectivity. Furthermore, olefin hydroamination as a synthetic approach is limited by the molecularity of the current methods with examples of the intermolecular variety being much rarer than the intramolecular. More recently, our group has helped to develop a general approach to olefin amination using catalytic N-H bond oxidation approaches. Although promising, the feasibility of this approach to olefin amination is currently limited by the amide substrate scope, in particular substrates other than para-methoxy-sulfonamide. Considering that, we developed an approach to improving the poor reactivity of N-H bond bearing sulfonamides by the appendage of additional electron-withdrawing functionality. A methodology for olefin hydroamination with secondary sulfonamides is highlighted as well to access a more diverse range of N-alkyl amides/amines through deprotection of the resulting N-alkyl amides.