The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins

• Alberto Luridiana^a, Daniele Mazzarella^a, Luca Capaldo^a, Juan A. Rincón^b, Pablo García-Losada^b, Carlos Mateos^b, Michael O. Frederick^c, Manuel Nuño^d, Wybren Jan Buma^e and Timothy Noël^a

• ^aFlow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
• ^bCentro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain
• ^cSmall Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, United States
• ^dVapourtec Ltd. Park Farm Business Centre, Fornham St Genevieve, Bury St Edmunds, Suffolk IP28 6TS, U.K.
• ^eMolecular Photonics, Van’t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp³)–C(sp²) and C(sp³)–C(sp³) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.

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