RESUMO
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.
RESUMO
We report a new pure-shift method, termed SHARPER (Sensitive, Homogeneous, And Resolved PEaks in Real time) designed for the analysis of reactions and equilibria by NMR. By focusing on a single selected signal, SHARPER removes all heteronuclear couplings of a selected nucleus without the need to pulse on X channels, thus overcoming hardware limitations of conventional spectrometers. A more versatile decoupling scheme, termed sel-SHARPER, removes all heteronuclear and homonuclear couplings of the selected signal. Both methods are characterized by a periodic inversion of the active spin during the real-time acquisition. In addition to decoupling, they also compensate for pulse imperfections and magnetic field inhomogeneity, generating an extremely narrow singlet with a linewidth approaching limits dictated by the spin-spin relaxation. The decoupling and line narrowing effected by (sel)-SHARPER provide significant increases in the signal-to-noise (S/N) ratio. Increases of 20-fold were routinely achieved for 19F detection. sel-SHARPER is also applicable to first- and higher-order 1H spectra. The sensitivity gains are substantially greater for inhomogeneous magnetic fields, including dynamic inhomogeneity caused by gas sparging. The parameters of the pulse sequences have been analyzed in detail to provide guidelines for their most effective application. The considerable reduction in the detection threshold induced by (sel)-SHARPER make the technique particularly suited for in situ monitoring of reaction kinetics. The approach is illustrated by a 19F NMR study of the protodeboronation of an aryl boronic acid. Here, the high S/N allowed reliable determination of the net protodeoboronation kinetics, and the excess line broadening of 19F singlets was utilized to characterize the boronic acid/boronate equilibrium kinetics. Oxidation of diphenylphosphine, monitored by 31P NMR under optimized gas-flow conditions, demonstrated the high tolerance of SHARPER to dynamic inhomogeneity. The principles of the (sel)-SHARPER sequences are expected to find numerous applications in the design of new NMR experiments.
