Anion-Initiated Trifluoromethylation by TMSCF: Deconvolution of the Siliconate-Carbanion Dichotomy by Stopped-Flow NMR/IR.

The mechanism of CF transfer from RSiCF (R = Me, Et, iPr) to ketones and aldehydes, initiated by MX (<0.004 to 10 mol %), has been investigated by analysis of kinetics (variable-ratio stopped-flow NMR and IR), C/H 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 (RSiCF) and initiator (MX). Traces of exogenous inhibitors present in the RSiCF 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 CF anion act as chain carriers in an anionic chain reaction. Silyl enol ether generation competes with 1,2-addition and involves protonation of CF by the α-C-H of the ketone and the OH of the enol. The overarching mechanism for trifluoromethylation by RSiCF, in which pentacoordinate siliconate intermediates are unable to directly transfer CF as a nucleophile or base, rationalizes why the turnover rate (per MX initiator) depends on the initial concentration (but not identity) of X, the identity (but not concentration) of M, the identity of the RSiCF reagent, and the carbonyl/RSiCF ratio. It also rationalizes which RSiCF reagent effects the most rapid trifluoromethylation, for a specific MX initiator.