Diversity-Oriented Synthesis of Azepinoindoles through sp ³ C–H Functionalization and Skeletal Remodeling

Molecular editing of N-heterocycles represents a powerful strategy for enhancing compound complexity and structural diversity at a late stage. However, combining both peripheral and skeletal editing of pyrrolidines for the diversity-oriented synthesis of azepinoindoles remains underexplored yet challenging. Herein, we report the ethanol-mediated redox sp³ C-H functionalization of pyrrolidines via the <i>tert</i>-amino effect and trifluoroacetic acid-promoted skeletal remodeling involving pyrrolidine ring expansion, which enables the divergent synthesis of azepino[4,3,2-<i>cd</i>]indoles and azepino[2,3-<i>e</i>]indoles. This method expands the scope of molecular editing of pyrrolidines, featuring metal-free reaction conditions, excellent functional group compatibility, late-stage modification of drug molecules, scalability, operational simplicity, and product derivatization. The mechanistic studies corroborate the proposed reaction pathway.