Desymmetrization and Atroposelective Cobalt Catalyzed C-H Annulation of Phosphinic Amides with Ynamides

Metal-catalyzed asymmetric C-H annulation enables enantioselective synthesis from simple precursors, but methods that simultaneously generate multiple stereogenic elements in a single step remain rare. We report the first Co(II)/Salox-catalyzed desymmetrizing atroposelective C-H annulation of phosphinic amides with ynamides, simultaneously generating a P-stereogenic center and C-C/C-N chiral axes in high yield and enantioselectivity (up to 87% yield, >99% ee). Notably, this catalytic system shows a substrate-dependent stereochemical outcome at the C-N axis, which is significant and nontrivial. DFT calculations are consistent with the experimentally observed stereochemical outcome and support a plausible model for stereocontrol. This work provides a valuable platform for the asymmetric synthesis of structurally and stereochemically complex organophosphorus compounds.