Alcohols as Alkylating Agents: Photoredox-Catalyzed Conjugate Alkylation via In Situ Deoxygenation

Johnny Z. Wang, Holt A. Sakai, David W.C. MacMillan

Research output: Contribution to journalArticlepeer-review

Abstract

The rapid exploration of sp3-enriched chemical space is facilitated by fragment-coupling technologies that utilize simple and abundant alkyl precursors, among which alcohols are a highly desirable, commercially accessible, and synthetically versatile class of substrate. Herein, we describe an operationally convenient, N-heterocyclic carbene (NHC)-mediated deoxygenative Giese-type addition of alcohol-derived alkyl radicals to electron-deficient alkenes under mild photocatalytic conditions. The fragment coupling accommodates a broad range of primary, secondary, and tertiary alcohol partners, as well as structurally varied Michael acceptors containing traditionally reactive sites, such as electrophilic or oxidizable moieties. We demonstrate the late-stage diversification of densely functionalized molecular architectures, including drugs and biomolecules, and we further telescope our protocol with metallaphotoredox cross-coupling for step-economic access to sp3-rich complexity.

Original languageEnglish (US)
Article numbere202207150
JournalAngewandte Chemie - International Edition
Volume61
Issue number35
DOIs
StatePublished - Aug 26 2022

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • Alcohols
  • Conjugate Addition
  • Deoxygenation
  • Photoredox

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