One‐Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp<sup>3</sup> C−H Imination
Subrata Ghosh, Mengnan Hu, Robert J. Comito
Abstract
Abstract The direct replacement of sp 3 C−H bonds with simple amine units (−NH 2 ) remains synthetically challenging, although primary aliphatic amines are ubiquitous in medicinal chemistry and natural product synthesis. We report a mild and selective protocol for preparing primary and secondary aliphatic amines in a single pot, based on intermolecular sp 3 C−H imination. The first C−H imination of diverse alkanes, this method shows useful site‐selectivity within substrates bearing multiple sp 3 C−H bonds. Furthermore, this reaction tolerates polar functional groups relevant for complex molecule synthesis, highlighted in the synthesis of amine pharmaceuticals and amination of natural products. We characterize a unique C−H imination mechanism based on radical rebound to an iminyl radical, supported by kinetic isotope effects, stereoablation, resubmission, and computational modeling. This work constitutes a selective method for complex amine synthesis and a new mechanistic platform for C−H amination.