Directed β C-H Amination of Alcohols via Radical Relay Chaperones

A radical-mediated strategy for beta C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the beta carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their beta-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.