Radical Redox Annulations: A General Light-Driven Method for the Synthesis of Saturated Heterocycles

Philip R.D. Murray, Isabelle Nathalie Marie Leibler, Sandrine M. Hell, Eris Villalona, Abigail G. Doyle, Robert R. Knowles

Research output: Contribution to journalArticlepeer-review

Abstract

We introduce here a 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.

Original languageEnglish (US)
Pages (from-to)13732-13740
Number of pages9
JournalACS Catalysis
Volume12
Issue number21
DOIs
StatePublished - Nov 4 2022

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • PCET
  • annulation
  • carbocations
  • heterocycles
  • photocatalysis

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