Copper-Catalyzed Radical Halocyclization of N-4-Pentenamides: Synthesis of Chloro- and Bromo-Substituted γ-Lactams

Halogenated γ-lactams are valuable synthetic targets, but efficient methods for accessing chloro- and bromo-substituted analogues remain elusive. Here we describe a copper-catalyzed radical halocyclization of N-4-pentenamides that enables one-step access to chloro- and bromo-substituted γ-lactams using inexpensive tetrabutylammonium chloride (TBACl) and tetraethylammonium bromide (TEAB) as halogen sources. The reactions proceed under mild conditions to afford desired products in good to excellent yields with a broad substrate scope and functional group tolerance. Preliminary mechanistic studies suggest a radical pathway involving a Cu(I)/Cu(II)/Cu(III) catalytic cycle and 5-exo-trig cyclization.