Anion-Initiated Trifluoromethylation by TMSCF 3 : Deconvolution of the Siliconate-Carbanion Dichotomy by Stopped-Flow NMR/IR.

The mechanism of CF ₃ transfer from R ₃ SiCF ₃ (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), ¹³ C/ ² 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 (R ₃ SiCF ₃ ) and initiator (M ⁺ X ^- ). Traces of exogenous inhibitors present in the R ₃ SiCF ₃ 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 ₃ ^- anion act as chain carriers in an anionic chain reaction. Silyl enol ether generation competes with 1,2-addition and involves protonation of CF ₃ ^- by the α-C-H of the ketone and the OH of the enol. The overarching mechanism for trifluoromethylation by R ₃ SiCF ₃ , in which pentacoordinate siliconate intermediates are unable to directly transfer CF ₃ ^- 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 R ₃ SiCF ₃ reagent, and the carbonyl/R ₃ SiCF ₃ ratio. It also rationalizes which R ₃ SiCF ₃ reagent effects the most rapid trifluoromethylation, for a specific M ⁺ X ^- initiator.