Enantioselective nucleophile-catalyzed synthesis of tertiary alkyl fluorides via the α-Fluorination of ketenes: Synthetic and mechanistic studies

Sarah Yunmi Lee, Stefan Neufeind, Gregory C. Fu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C 6F5ONa) is critical for turnover, releasing the catalyst (PPY) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N- acylpyridinium salt, have been examined.

Original languageEnglish
Pages (from-to)8899-8902
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number25
DOIs
Publication statusPublished - 2014 Jun 25

All Science Journal Classification (ASJC) codes

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

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