A Tale of Two Hydroaminations: Development of Two Novel Reactions for Alkene Hydroamination Enabled by Proton-Coupled Electron Transfer

Abstract

Herein, we describe the development of a new reaction for the anti-Markovnikov hydroamination of unactivated olefins with sulfonamides catalyzed by proton-coupled electron transfer (PCET). Substrate scope studies show that the reaction is capable of achieving both intra- and intermolecular hydroaminations and is widely tolerant of both the sulfonamide and olefin substitution patterns. Mechanistic investigations revealed that the key step in the reaction is a PCET-mediated homolysis of the sulfonamide N–H bond by the excited-state iridium photocatalyst and phosphate base. This reaction presents a simple route to anti-Markovnikov hydroamination products, a longstanding challenge in organic synthesis. Furthermore, the procedure demonstrates the capability of PCET to activate the strong bonds of common organic functional groups in a chemoselective and kinetically facile manner. We also report preliminary efforts towards a protocol for the catalytic asymmetric hydroamination of olefins with sulfonamides. This reaction is achieved through a similar protocol to the racemic hydroamination, with the substitution of a chiral phosphate base for the original achiral base. Initial work has shown that the reaction an effect intramolecular hydroaminations for a variety of olefin substitution patterns with high selectivity. Early efforts to describe the physical organic parameters of the optimal chiral phosphate base are also reported.