Mechanism and origin of stereoselectivity and regioselectivity in cobalt-catalyzed C–H functionalization of arylphosphinamide†

The cobalt-catalyzed C–H functionalization of arylphosphinamides is a promising strategy for constructing P-containing scaffolds but has been mechanistically underexplored. We perform a density functional theory (DFT) study to elucidate the mechanism and origins of selectivities for this transformation. The computational results reveal a stepwise pathway involving sequential N–H and C–H activation followed by alkyne insertion and reductive elimination. The C–H cleavage and alkyne insertion are identified as the stereoselectivity-determining processes, and alkyne insertion is identified as the regioselectivity-determining step. The pronounced S-selectivity arises from a larger number of noncovalent interactions in the low-energy transition state compared with the higher energy transition state. The regioselectivity is determined using a frontier molecular orbital (FMO) analysis. The results of this study provide valuable insights into the underlying chemistry of the Co-catalyzed C–H functionalization of arylphosphinamide.