Direct nucleophilic trifluoromethylation using fluoroform: a theoretical mechanistic investigation and insight into the effect of alkali metal cations

Abstract

Prakash and co-workers recently reported a direct trifluoromethylation of Si, B, S, and C centers using fluoroform (CF₃H) and dramatic effects of alkali metal salts of hexamethyldisilazane in this reaction (Science, 2012, 338, 1324). Herein, the detailed mechanisms of trifluoromethylation of Si and C centers in the presence of (Me₃Si)₂NK as a base have been studied using the DFT method. It has been found that the origin of the dramatic effect of the alkali metals is the stability of an intermediate MCF₃. More interestingly, a linear relationship has been found between the chemical hardness of M⁺ (M = Li, Na, K, Rb, Cs) and the difference between the values of ΔG_dec and ΔG_tfm (ΔG_dec, decomposition energy of the key intermediate MCF₃; ΔG_tfm, relative energy barrier for the formation of a Si–CF₃ or C–CF₃ bond). These results may help to both theoretically and experimentally search for better bases to develop more atom-economic and environmentally benign protocols to achieve trifluoromethylation using CF₃H.