Research ArticleChemistry

Ketones and aldehydes as alkyl radical equivalents for C─H functionalization of heteroarenes

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Science Advances  11 Oct 2019:
Vol. 5, no. 10, eaax9955
DOI: 10.1126/sciadv.aax9955


The polar nature of the C═O bond commonly allows it to undergo direct attack by nucleophiles at the electrophilic carbon atom in which ketones and aldehydes act as alkyl carbocation equivalents. In contrast, transformations in which ketones and aldehydes act as alkyl radical equivalents (generated in carbonyl carbon) are unknown. Here, we describe a new catalytic activation mode that combines proton-coupled electron transfer (PCET) with spin-center shift (SCS) and enables C─H alkylation of heteroarenes using ketones and aldehydes as alkyl radical equivalents. This transformation proceeded via reductive PCET activation of the ketones and aldehydes to form α-oxy radicals, addition of the radicals to the N-heteroarenes to form C─C bonds, and SCS to cleave the C─O bonds of the resulting alcohols. This mild protocol represents a general use of abundant, commercially available, ketones and aldehydes as latent alkyl radical equivalents.

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