Redox-Neutral Cu-Catalyzed Cyclative γ-C-H Functionalization Enroute to Aza- and Oxo-heterocycles.

Cyclative C(sp3)-H functionalization of unactivated C─H bonds with heteroatoms is a straightforward way to construct saturated aza- and oxo-heterocycles, which continues to display ever-increasing prevalence in drug design. Building upon our recently reported copper catalysis that used simple N-methoxyamides as radical precursors, we report a method to access diverse aza- and oxo-heterocycles, including cyclic sulfonamides, cyclic ethers, and lactones of different ring sizes. By placing a heteroatom in the N-methoxyamide substrate, the carbon radical formed at the γ-position from the intramolecular H-abstraction by the amidyl radical could be trapped with the pendant heteroatom, leading to a redox-neutral Cu-catalyzed cyclative γ-C(sp3)-H functionalization. The syntheses of a wide range of saturated aza- and oxo-heterocycles demonstrate the versatility of this method.