Reversal of Regioselectivity in Asymmetric C-H Bond Annulation with Bromoalkynes under Cobalt Catalysis

Metal-catalyzed asymmetric C-H bond annulation strategy offers a versatile platform, allowing the construction of complex P-chiral molecules through atom- and step-economical fashion. However, regioselective insertion of π-coupling partner between M-C bond with high enantio-induction remain elusive. Using commercially available Co(II) salt and chiral-Salox ligands, we demonstrate an unusual protocol for the regio-reversal, enantioselective C-H bond annulation of phosphinamide with bromoalkyne through desymmetrization. The reaction proceeds through ligand-assisted enantiodetermining cyclocobaltation followed by regioselective insertion of bromoalkyne between Co-C, subsequent reductive elimination, and halogen exchange with carboxylate resulted in P-stereogenic compounds in excellent ee (up to >99 %). The isolation of cobaltacycle involved in the catalytic cycle and the outcome of control experiments provide support for a plausible mechanism.