Flow photochemical Giese reaction via silane-mediated activation of alkyl bromides

• Fabiola Fanini^ab, Alberto Luridiana^a, Daniele Mazzarella^ac, Antonella Ilenia Alfano^ad, Perryvan der Heide^a, Juan A. Rincón^e, Pablo García-Losada^e, Carlos Mateos^e, Michael O. Frederick^f, Manuel Nuño^g, 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
• ^bDepartment of Biomolecular Sciences, University of Urbino “Carlo Bo”, Piazza Rinascimento 6, I-61029 Urbino, Italy
• ^cDepartment of Chemical Sciences, University of Padova Institution, Via Francesco Marzolo, 1, 35131 Padova, Italy
• ^dDepartment of Pharmacy, Department of Excellence 2018-2022, School of Medicine and Surgery, University of Naples “Federico II”, Via D. Montesano 49, I-80131 Naples, Italy
• ^eCentro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain
• ^fSmall Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, United States
• ^gVapourtec Ltd. Park Farm Business Centre, Fornham St Genevieve, Bury St Edmunds, Suffolk IP28 6TS, United Kingdom

Organic halides play a key role as building blocks in synthesis because of their low cost and wide availability. In recent years, halogen-atom transfer (XAT) has emerged as a reliable approach to exploit these substrates in radical processes. Herein, we report a hydroalkylation of electron-poor olefins using alkyl bromides based on a UVA-induced silane-mediated XAT reaction. Our protocol is operationally simple, displays a broad scope and does not require a photocatalyst. Flow technology was used to reduce the reaction times and scale the process. Notably, a two-step protocol, combining the XAT protocol with a subsequent Horner-Wadsworth-Emmons reaction, has been developed to enable the allylation of C(sp3)–Br bonds.

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