Photoredox-catalyzed, oxygen-directed unactivated δ-C(sp3)–H functionalization toward oxepanes

Abstract

Oxepane motifs are prevalent in both naturally and synthetically bioactive molecules. We report herein a photoredox-catalyzed formal [5 + 2] annulation of N-alkoxypyridiniums and 1,3-dienes/1,3-enynes for rapid synthesis of structurally diverse alkene/alkyne-containing oxepanes. The reaction features selective functionalization of distal unactivated C(sp³)–H bonds and a broad substrate scope, thus allowing the transformation of complex natural products. A radical mechanism involving oxygen-directed 1,5-hydrogen atom transfer, facile coupling of alkyl radicals with 1,3-dienes/1,3-enynes, and the construction of oxepane motifs via C–O bond formation is proposed.