C–H/C–C Functionalization Approach to N‑Fused Heterocycles from Saturated Azacycles

Herein we report the synthesis of substituted indolizidines and related N-fused bicycles from simple saturated cyclic amines through sequential C–H and C–C bond functionalizations. Inspired by the Norrish–Yang Type II reaction, C–H functionalization of azacycles is achieved by forming α-hydroxy-β-lactams from precursor α-ketoamide derivatives under mild, visible light conditions. Selective cleavage of the distal C­(sp2)–C­(sp3) bond in α-hydroxy-β-lactams using a Rh-complex leads to α-acyl intermediates which undergo sequential Rh-catalyzed decarbonylation, 1,4-addition to an electrophile, and aldol cyclization, to afford N-fused bicycles including indolizidines. Computational studies provide mechanistic insight into the observed positional selectivity of C–C cleavage, which depends strongly on the groups bound to Rh trans to the phosphine ligand.