Anion-Initiated trifluoromethylation by TMSCF3 : deconvolution of the siliconate-carbanion dichotomy by stopped-flow NMR/IR

Johnston, Craig P. and West, Thomas H. and Dooley, Ruth E. and Reid, Marc and Jones, Ariana B. and King, Edward J. and Leach, Andrew G. and Lloyd-Jones, Guy C. (2018) Anion-Initiated trifluoromethylation by TMSCF3 : deconvolution of the siliconate-carbanion dichotomy by stopped-flow NMR/IR. Journal of the American Chemical Society, 140 (35). pp. 11112-11124. ISSN 0002-7863 (https://doi.org/10.1021/jacs.8b06777)

[thumbnail of Johnston-etal-JACS2018-Anion-Initiated-trifluoromethylation-TMSCF3-deconvolution-siliconate-carbanion-dichotomy-stopped-flow-NMR-IR]
Preview
 Text. Filename: Johnston_etal_JACS2018_Anion_Initiated_trifluoromethylation_TMSCF3_deconvolution_siliconate_carbanion_dichotomy_stopped_flow_NMR_IR.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo
Download (3MB)| Preview

Abstract

The mechanism of CF3 transfer from R3SiCF3 (R = Me, Et, iPr) to ketones and aldehydes, initiated by M+X- (<0.004 to 10 mol %), has been investigated by analysis of kinetics (variable-ratio stopped-flow NMR and IR), 13C/2H KIEs, LFER, addition of ligands (18-c-6, crypt-222), and density functional theory calculations. The kinetics, reaction orders, and selectivity vary substantially with reagent (R3SiCF3) and initiator (M+X-). Traces of exogenous inhibitors present in the R3SiCF3 reagents, which vary substantially in proportion and identity between batches and suppliers, also affect the kinetics. Some reactions are complete in milliseconds, others take hours, and others stall before completion. Despite these differences, a general mechanism has been elucidated in which the product alkoxide and CF3 - anion act as chain carriers in an anionic chain reaction. Silyl enol ether generation competes with 1,2-addition and involves protonation of CF3 - by the α-C-H of the ketone and the OH of the enol. The overarching mechanism for trifluoromethylation by R3SiCF3, in which pentacoordinate siliconate intermediates are unable to directly transfer CF3 - as a nucleophile or base, rationalizes why the turnover rate (per M+X- initiator) depends on the initial concentration (but not identity) of X-, the identity (but not concentration) of M+, the identity of the R3SiCF3 reagent, and the carbonyl/R3SiCF3 ratio. It also rationalizes which R3SiCF3 reagent effects the most rapid trifluoromethylation, for a specific M+X- initiator.

  • Item type:Article
    ID code:86745
    Dates:
    Date
    Event
    5 September 2018
    Published
    6 August 2018
    Published Online
    5 August 2018
    Accepted
    27 June 2018
    Submitted
    Notes:Publisher Copyright: © 2018 American Chemical Society. Anion-Initiated Trifluoromethylation by TMSCF3: Deconvolution of the Siliconate–Carbanion Dichotomy by Stopped-Flow NMR/IR, Craig P. Johnston, Thomas H. West, Ruth E. Dooley, Marc Reid, Ariana B. Jones, Edward J. King, Andrew G. Leach, and Guy C. Lloyd-Jones, Journal of the American Chemical Society 2018 140 (35), 11112-11124, DOI: 10.1021/jacs.8b06777
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:21 Sep 2023 12:57
    Last modified:26 Apr 2024 01:03
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/86745
CORE (COnnecting REpositories)