Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis

Jack Twilton, Melodie Christensen, Daniel A. DiRocco, Rebecca T. Ruck, Ian W. Davies, David W.C. MacMillan

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α-hydroxy C−H bonds. This approach employs zinc-mediated alcohol deprotonation to activate α-hydroxy C−H bonds while simultaneously suppressing C−O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn-based Lewis acids also deactivates other hydridic bonds such as α-amino and α-oxy C−H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3-step synthesis of the drug Prozac exemplifies the utility of this new method.

Original languageEnglish (US)
Pages (from-to)5369-5373
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number19
DOIs
StatePublished - May 4 2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • alcohols
  • heterocycles
  • hydrogen atom transfer
  • nickel
  • photoredox catalysis

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