One-Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp C-H Imination.

The direct replacement of sp C-H bonds with simple amine units (-NH ) 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 C-H imination. The first C-H imination of diverse alkanes, this method shows useful site-selectivity within substrates bearing multiple sp 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.