title: Computational SN 2-Type Mechanism for the Difluoromethylation of Lithium Enolate with Fluoroform through Bimetallic C-F Bond Dual Activation.
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 SN 2-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.
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, Tokyo, 152-8552, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto, 606-8103, Japan.|Department of Chemistry, University of Puget Sound, Tacoma, Washington, 98416, USA.
authors.forename: Travis V
authors.initials: TV
authors.lastname: Harris
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto, 606-8103, Japan.|Department of Chemistry, Faculty of Science and Engineering, Kinki University, Osaka, 577-8502, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hatanaka
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto, 606-8103, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Morokuma
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, Tokyo, 152-8552, Japan. mikami.k.ab@m.titech.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mikami
keywords: carbenoids; computational chemistry; fluorine; nucleophilic substitution; reaction mechanisms