Long‐Lived Trifluoromethanide Anion: A Key Intermediate in Nucleophilic Trifluoromethylations

Abstract

The trifluoromethanide anion is the postulated key intermediate in nucleophilic trifluoromethylation reactions. However, for more than six decades, the trifluoromethanide anion was widely believed to exist only as a short-lived transient species in the condensed phase. It has now been prepared in bulk for the first time in THF solution. The trifluoromethanide anion with the [K(18-crown-6)](+) cation was unequivocally characterized by low-temperature (19)F and (13)C NMR spectroscopy. Its intermediacy in nucleophilic trifluoromethylation reactions was directly evident by its reaction chemistry with various electrophilic substrates. Variable-temperature NMR spectroscopy, along with quantum mechanical calculations, support the persistence of the trifluoromethanide anion.

Computational Insights into Nucleophilic Copper-Catalyzed Trifluoromethylation of Aryl Halides

“…CF 3 -) could remain stable in solvent at low temperatures. 24 In this line the calculations indicate that this decomposition is not as easy as expected since it is endergonic by almost 9 kcal mol -1 .…”

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

“…Given the importance and high demand of CF 3 -substituted heterocycles in synthetic organic, medicinal, and agrochemical chemistry, there will be an ever-growing inventory of new synthetic strategies. Among future research of great interest will be the development of new asymmetric trifluoromethylation strategies with cheap reagents, [107] prochiral trifluoromethyl substrates, as well as the development of novel privileged catalysts that are able to address the challenge in catalytic asymmetric protocols for the construction of enantiopure trifluoromethylated heterocyclic frameworks with wide structural and functional diversity. In the meantime, the discovery of new drugs and agrochemicals bearing a chiral CF 3 -heterocyclic skeleton will further stimulate attempts to create novel catalytic asymmetric approaches.…”

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“…As a matter of fact, Mg and LiCF 3 reagents spontaneously eliminate fluoride, with enough energy released to be con sidered explosive. 3,4 This inherent instability has hindered progress in the development of new trifluoromethylation methodologies; indeed, ninety years passed between the first nucleophilic methylations 5 and the first efficient nucleophilic trifluoromethylations." 6 The group of Professor Szymczak re cently designed a new approach to CF 3 -reagents from an in dustrial waste gas.…”