Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution

Colin A. Gould, Andria L. Pace, David W.C. MacMillan

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Quaternary carbons are ubiquitous in bioactive molecules; however, synthetic methods for the construction of this motif remain underdeveloped. Here, we report the synthesis of quaternary carbons from tertiary alcohols, a class of structurally diverse, bench-stable feedstocks, via the merger of photoredox catalysis and iron-mediated SH2 bond formation. This alcohol-bromide cross-coupling is enabled by a novel halogen-atom transfer (XAT) reagent, which is the first reductively activated XAT reagent to be reported. A wide variety of sterically congested quaternary products can be accessed through this mild and practical protocol including products derived from both alkylation and benzylation of tertiary fragments. We further demonstrate the synthetic utility of this method through the expedited synthesis of a liver receptor agonist and through a two-step conversion of ketones and esters to quaternary products, which enables the modular control of up to three of the four substituents on a quaternary center.

Original languageEnglish (US)
Pages (from-to)16330-16336
Number of pages7
JournalJournal of the American Chemical Society
Volume145
Issue number30
DOIs
StatePublished - Aug 2 2023

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry

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