Dehydrogenative Coupling of Alcohols with Internal Alkynes under Nickel Catalysis: An Access to β-Deuterated Branched Ketones

Abstract

In synthetic organic chemistry, unconventional strategies for advanced chemical synthesis pose interesting and challenging problems. Alcohols act as alkylating agents in the C–C and C–N bond-forming reactions via the dehydrogenative borrowing hydrogen strategy in traditional transition metal catalysis; however, as an acylating agent in the C–C bond-forming reactions is challenging and rarely reported. Here, we report the dehydrogenative coupling of benzylic alcohols with internal alkynes under nickel(II) catalysis, wherein alcohol is used as an acylating agent. This reaction system affords a wide range of α-branched aryl ketone derivatives with zero waste generation through the umpolung borrowing hydrogen strategy. Moreover, we have demonstrated the chemodivergent applications of the α-disubstituted ketones to other valuable building blocks, including large-scale synthesis of β-deuterated branched ketones. Several spectroscopic studies, intermediate identification, and density functional theory calculations were performed to elucidate the reaction mechanism.