Cobalt-catalyzed enantioselective desymmetrizing reductive cyclization of alkynyl cyclodiketones

A highly enantioselective cobalt-catalyzed desymmetrizing reductive cyclization of alkynyl cyclodiketones has been developed. Under mild reaction conditions by employing HBpin as a reducing agent and ferrocene-based PHOX as a chiral ligand, a series of polycyclic tertiary allylic alcohols bearing contiguous quaternary stereocenters are achieved in moderate to excellent yields with excellent enantioselectivities (up to 99%). Broad substrate scope and high functional group compatibility are observed in this reaction. A CoH-catalyzed pathway involving alkyne hydrocobaltation followed by nucleophilic addition to the C00000000000000000000000000000000111111110000000011111111000000000000000000000000O bond is proposed. Synthetic transformations of the product are conducted to demonstrate the practical utilities of this reaction.

Automated summary

A highly enantioselective cobalt-catalyzed desymmetrizing reductive cyclization of alkynyl cyclodiketones has been developed. This reaction utilizes HBpin as a reducing agent and ferrocene-based PHOX as a chiral ligand to achieve moderate to excellent yields of polycyclic tertiary allylic alcohols with excellent enantioselectivities (up to 99%). The reaction demonstrates broad substrate scope, high functional group compatibility, and a proposed CoH-catalyzed pathway.