Copper-Catalyzed γ-C(sp3)-H Lactamization and Iminolactonization.

Abstract

Despite extensive efforts to develop γ-lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C-H insertion, or radical C-H abstraction strategies, γ-lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper-catalyzed γ-C(sp3)-H lactamization and iminolactonization of tosyl-protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ-Lactams or γ-iminolactones can be obtained by using two different sets of reaction conditions. Notably, structurally diverse spiro-, fused-, and bridged-lactams and iminolactones, as well as isoindolinones are accessible by this method. Further derivatization of the γ-lactam products enables the synthesis of a range of biologically important motifs, including γ-amino acids, δ-amino alcohols, and pyrrolidines.