Radical redox cycloadditions: a general light-driven method for the synthesis of saturated heterocycles Philip Murray 1 , Isabelle N.M. Leibler 1 , Sandrine M. Hell 1 , Eris Villalona 1 , Abigail G. Doyle 2 , Robert R. Knowles 1 1 University of Cambridge, UK, 1 Princeton University, USA, 2 University of California, USA In this work, we introduce here a novel two-component annulation strategy that provides access to a diverse collection of five- and six-membered saturated heterocycles from aryl alkenes and a family of redox-active radical precursors bearing tethered nucleophiles. This transformation is mediated by a combination of an Ir(III) photocatalyst and a Brønsted acid under visible-light irradiation. A reductive proton-coupled electron transfer generates a reactive radical which undergoes addition to an alkene. Then, an oxidative radical-polar crossover step leading to carbocation formation is followed by ring closure through cyclization of the tethered nucleophile. A wide range of heterocycles are easily accessible, including pyrrolidines, piperidines, tetrahydrofurans, morpholines, δ-valerolactones, and dioxanones. We demonstrate the scope of this approach through broad structural variation of both reaction components. This method is amenable to gram-scale preparation and to complex fragment coupling. References 1. Murray P.R.D.,Leibler I.N.M.,Hell S.M.,Villalona, E.,Doyle A.G., and Knowles R.R., Radical Redox Cycloadditions: A General Light-Driven Method for the Synthesis of Saturated Heterocycles, ChemRxiv , 2022 .DOI:10.26434/chemrxiv-2022-4h5kq.
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