Deacylative arylation and alkynylation of unstrained ketones
B. L. Zhang, Hui Bai, Bei‐Bei Zhan, Kaihang Wei, Shenyou Nie, Xiaheng Zhang
Abstract
Ketones are ubiquitous in bioactive natural products, pharmaceuticals, chemical feedstocks, and synthetic intermediates. Hence, deacylative coupling reactions enable the versatile elaboration of a plethora of chemicals to access complex drug candidates and natural products. Here, we present deacylative arylation and alkynylation strategies for the synthesis of a wide range of alkyl-tethered arenes and alkynes from cyclic ketones and methyl ketones under dual nickel/photoredox catalysis. This reaction begins by generating a pre-aromatic intermediate (PAI) through the condensation of the ketone and N ′-methylpicolino-hydrazonamide (MPHA), followed by the oxidative cleavage of the PAI α-C─C bond to form an alkyl radical, which is subsequently intercepted by a Ni complex, facilitating the formation of diverse C( sp 3 )–C( sp 2 )/C( sp ) bonds with remarkable generality. This protocol features a one-pot reaction capability, high regioselectivity and ring-opening efficiency, mild reaction conditions, and a broad substrate scope with excellent functional group compatibility.