Nitrogen-directed unactivated γ-C(sp3)–H functionalization of amides toward 7-membered lactones via photoredox catalysis

Abstract

Lactone motifs are prevalent in both naturally and synthetically bioactive molecules. We report herein a photoredox-catalyzed formal [5 + 2] annulation of O-acylhydroxamide derivatives with 1,3-dienes/1,3-enynes for the rapid synthesis of structurally diverse alkene/alkyne-containing 7-membered lactones. The reaction features selective transformation of distal unactivated C(sp³)–H bonds and a good substrate scope. A radical mechanism involving nitrogen-directed 1,5-hydrogen atom transfer (HAT) and facile coupling of alkyl radicals with 1,3-dienes/1,3-enynes, leading to the construction of 7-membered lactone motifs via C–O bond formation is proposed.