Trifluoromethyl anion: Generation, stability, and SNAr reactivity in crown ether complex analyzed by theoretical calculations

Abstract

The trifluoromethyl anion is a reactive species useful for the trifluoromethylation reaction of organic compounds. However, this species is prone to an elimination process via the generation of CF2 or reaction with water or alcohols by protonation, limiting its potential application in synthesis. Complexation of the in situ generated KCF3 salt with crown ethers increases its stability. In this work, we have investigated theoretically the generation, stability, and SNAr reactivity of the CF3− anion in the K+(18-crown-6)(CF3−) complex towards different substrates. Our results point out that the TESCF3 reagent is a good source of the CF3− anion under reaction with potassium methoxide, whereas the HCF3 species is less effective. The formal elimination of CF2 takes place via the [K+(18-crown-6)(CF3−)]2 dimeric species with overall ΔG‡ = 18.7 kcal mol−1, and the transient carbene interacts with another CF3− forming CF2CF3−. Six substrates were investigated for the SNAr reaction with K+(18-crown-6)(CF3−) complex. The reaction with phenyl bromide is very unfavorable, with ΔG‡ = 29.7 kcal mol−1. Two activating groups such as CN in the ortho and para positions are needed to produce an enough low barrier of ΔG‡ = 14.2 kcal mol−1, able to compete with the decomposition of the CF3− anion.