Direct Trifluoromethylation of Nitriles Promoted by Tetrabutylammonium Bifluoride

Abstract

The direct trifluoromethylation of nitriles using TMSCF₃ is reported. This reaction is promoted by TBABF and provides α,α-bistrifluoromethylated amines in moderate to good yields. The reaction conditions are mild and tolerate a range of functional groups. The X-ray crystal structure of a bistrifluoromethylamine was obtained.

α,α-bistrifluoromethylated amines - nitriles - tetrabutyl-ammonium bifluoride - trifluoromethyltrimethylsilane

References and Notes

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Typical Procedure for Trifluoromethylation of Various Nitriles Promoted by TBABF
Biphenyl-4-carbonitrile (110 mg, 0.61 mmol) was dissolved in THF (4 mL). Under nitrogen at 0 ˚C (trifluoromethyl)tri-methylsilane (0.45 mL, 3.05 mmol, 5 equiv) was added. To this mixture was then added TBAF˙HF (0.360 g, 1.28 mmol, 2.1 equiv) solution in THF (4 mL). The cooling bath was removed, and the reaction mixture was stirred at 25 ˚C for 2 h. The reaction mixture was concentrated under rotary vacuum to give a light yellow gum. Column chromatog-raphy of the residue (silica gel, hexane-EtOAc = 5:1) provided 2-biphenyl-4-yl-1,1,1,3,3,3-hexafluoropropan-2-amine (154 mg, 79%) as a white solid. ^¹H NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 8.3 Hz, 2 H), 7.63-7.69 (m, 2 H), 7.56-7.63 (m, 2 H), 7.42-7.50 (m, 2 H), 7.35-7.42 (m, 1 H), 2.20 (br s, 2 H). ^¹³C NMR (101 MHz, CDCl₃): δ = 143.2, 140.3, 129.7, 129.3, 128.3, 128.2, 127.7, 127.6, 124.3 (q, J = 286.9 Hz), 65.4 (spt, J = 27.8 Hz). HRMS (ESI⁺): m/z calcd for C₁₅H₁₂F₆N [M + H]⁺: 320.08684; found [M + H]⁺: 320.08670.

<A NAME="RS04909ST-18">18</A>

CCDC 729907 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

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