Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols

Eric D. Nacsa, David W.C. MacMillan

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

Original languageEnglish (US)
Pages (from-to)3322-3330
Number of pages9
JournalJournal of the American Chemical Society
Volume140
Issue number9
DOIs
StatePublished - Mar 7 2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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