Deacylative arylation and alkynylation of unstrained ketones

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.