Iodoarene-directed photoredox β-C(sp3)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer†
Abstract
Site selective functionalization of inert remote C(sp3)–H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical β-C(sp3)–H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)–H bond processes have been well developed. However, radical-mediated direct β-C(sp3)–H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox β-C(sp3)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical–radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)–H bonds like β-C(sp3)–H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)–H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical–radical coupling processes.
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