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

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 Delta G(double dagger) = 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 Delta G(double dagger) = 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 Delta G(double dagger) = 14.2 kcal mol(-1), able to compete with the decomposition of the CF3- anion.

Automated summary

The trifluoromethyl anion is a reactive species that is useful for organic synthesis, but its potential is limited due to its instability and susceptibility to elimination reactions. Complexation of the KCF3 salt with crown ethers can increase its stability. Theoretical investigations have been conducted on the generation, stability, and reactivity of the CF3- anion in the K+(18-crown-6)(CF3-) complex towards different substrates. The results indicate that TESCF3 is a good source of the CF3- anion, while HCF3 is less effective. The elimination of CF2 takes place via the dimeric species [K+(18-crown-6)(CF3-)](2) with a barrier energy of 18.7 kcal mol(-1), and the transient carbene interacts with another CF3- to form CF2CF3-. Six substrates were investigated for the SNAr reaction with the K+(18-crown-6)(CF3-) complex, and two activating groups are needed for a favorable reaction.