Computational SN2-Type Mechanism for the Difluoromethylation of Lithium Enolate with Fluoroform through Bimetallic C−F Bond Dual Activation

Kazuya Honda, Travis V. Harris, Miho Hatanaka, Keiji Morokuma, Koichi Mikami

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The reaction mechanism for difluoromethylation of lithium enolates with fluoroform was analyzed computationally (DFT calculations with the artificial force induced reaction (AFIR) method and solvation model based on density (SMD) solvation model (THF)), showing an SN2-type carbon–carbon bond formation; the “bimetallic” lithium enolate and lithium trifluoromethyl carbenoid exert the C−F bond “dual” activation, in contrast to the monometallic butterfly-shaped carbenoid in the Simmons–Smith reaction. Lithium enolates, generated by the reaction of 2 equiv. of lithium hexamethyldisilazide (rather than 1 or 3 equiv.) with the cheap difluoromethylating species fluoroform, are the most useful alkali metal intermediates for the synthesis of pharmaceutically important α-difluoromethylated carbonyl products.

Original languageEnglish
Pages (from-to)8796-8800
Number of pages5
JournalChemistry - A European Journal
Volume22
Issue number26
DOIs
Publication statusPublished - 2016

Keywords

  • carbenoids
  • computational chemistry
  • fluorine
  • nucleophilic substitution
  • reaction mechanisms

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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