Catalyst-Controlled Diastereoselective Synthesis of Cyclic Amines via C-H Functionalization

Reliable regio- and stereochemical techniques applicable to nonactivated aliphatic systems remain largely elusive due to the challenges of discriminating between multiple, relatively strong sp3 C–H bonds whose chemical behavior often differ only subtly. Nevertheless, approaches that employ directing groups and/or auxiliaries have emerged, but impose practical restrictions, especially in complex molecule synthesis. This report describes a catalyst-controlled regio- and diastereoselective synthesis of N-unprotected pyrrolidines via dirhodium catalyzed intramolecular nitrene insertion into sp3 C–H bonds. The reaction proceeds at rt without external oxidants, nitrene stabilizing groups, or directing functionality. The insights that emerged from the conformational/stereoselectivity relationships (CSR) between catalysts and substrates provide a framework for rational catalyst design that can accommodate a broader range of aliphatic C–H chemistry.