Mechanism ofC–SiBond Cleavage Using Lewis Bases (n→ σ*)

Anion-Initiated Trifluoromethylation by TMSCF3: Deconvolution of the Siliconate–Carbanion Dichotomy by Stopped-Flow NMR/IR

“…Which of these two pathways is followed in catalytic reactions at ambient temperature has been a long-standing mechanistic dichotomy. 30 A variable-ratio stopped-flow NMR/IR approach ( Figure 3 ) has been developed to facilitate time- and material-efficient analysis of a wide range of initiator (M + X – ) and reactant concentrations. Change of reagent from TMSCF 3 ( 1a ) to TIPSCF 3 ( 1c ) has a profound impact on the reaction.…”

“…Previous mechanistic work has focused on stoichiometric reactions of R 3 SiCF 3 ( 1a , c ) with anions at low temperatures, generating unstable trifluoromethyl siliconates ( C , D ) − and carbanion­(oids) ( E ), − depending on conditions. Which of these two pathways is followed in catalytic reactions at ambient temperature has been a long-standing mechanistic dichotomy . A variable-ratio stopped-flow NMR/IR approach (Figure ) has been developed to facilitate time- and material-efficient analysis of a wide range of initiator (M + X – ) and reactant concentrations.…”

“…For example, in the context of the design and analysis of enantioselective trifluoromethylation processes, ,,, mechanism V shows that control must be achieved by the CF 3 – /[M] + ion pair, Figure ii, and not by a siliconate intermediate. Moreover, the key mechanistic features of the anion-initiated reactions of 1 with carbonyl compounds (Figure ) translate to reactions of 1 with other electrophiles ( E ) − and proton donors (R–H to generate R – ), Figure . Thus, all processes in which siliconate D or analogous species formally acts as a nucleophilic or basic source of CF 3 must proceed via a dissociative pathway (Figure ii).…”

“…Thus, all processes in which siliconate D or analogous species formally acts as a nucleophilic or basic source of CF 3 must proceed via a dissociative pathway (Figure ii). Siliconate D is inherently unstable and decomposes at ambient temperature to generate, inter alia , complex perfluorocarbanions. , The rate of anionic chain transfer, as dictated by the reactivity of the electrophile ( E ) − or carbon acid (R–H) toward CF 3 – , as well as the presence of species able to attenuate decomposition (e.g., via CF 2 capture, 4 OSi → 10 , Scheme ), controls the formal lifetime of D and in turn the minimum loading of initiator (M + X – ) that will be required to achieve complete conversion of substrate. Moreover, traces of exogenous inhibitor(s) (e.g., Z–LG, Figure iii) ubiquitous in R 3 SiCF 3 reagents ( 1 ) act to reduce the net active anion in the chain reaction, again increasing the requisite loading of initiator (M + X – ).…”

“…Despite anion-initiated trifluoromethylation by 1a having become a mainstream synthetic method, − surprisingly little detail has emerged on the mechanism of CF 3 transfer, under the conditions of application, Scheme . Various mechanistic dichotomies, including, inter alia , fluoride initiation versus fluoride catalysis, and siliconate versus carbanion pathways, have been noted by Denmark and by Reich, both of whom emphasize the lack of salient kinetic data.…”