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.

Key words

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

References and Notes

• 1 See Special Issue, Fluorine in Life Sciences: ChemBioChem  2004,  5:  557 
• 2 Muller K. Faeh C. Diederich F. Science  2007,  317:  1881 
• 3 Hiyama T. In Organofluorine Compounds: Chemistry and Applications   Yamamoto H. Springer; New York: 2000. 
• 4 Reichenbächer K. Süss KI. Hulliger J. Chem. Soc. Rev.  2005,  34:  22 
• 5 Hagmann WK. J. Med. Chem.  2008,  51:  4359 
• 6 Prakash GKS. Yudin AK. Chem. Rev.  1997,  97:  757 
• 7 Zard SZ. Org. Biomol. Chem.  2007,  5:  205 
• 8 Prakash GKS. Krishnamurti R. Olah GA. J. Am. Chem. Soc.  1989,  111:  393 
• 9 Wiedmann J. Heiner T. Mloston G. Prakash GSK. Olah GA. Angew. Chem. Int. Ed.  1998,  37:  820 
• 10 Nelson DW. Owens J. Hiraldo D. J. Org. Chem.  2001,  66:  2572 
• 11 Prakash GKS. Mogi R. Olah GA. Org. Lett.  2006,  8:  3589 
• 12 Gale DM. Krespan CG. J. Org. Chem.  1968,  33:  1002 
• 13 Nesi M. Brasca MG. Longo A. Moretti W. Panzeri A. Tetrahedron Lett.  1997,  38:  4881 
• 14 Sun H. DiMagno SG. J. Am. Chem. Soc.  2005,  127:  2050 
• 15 Sharma RK. Fry JL. J. Org. Chem.  1983,  48:  2112 
• 16 Bosh P. Camps F. Chamarro E. Tetrahedron Lett.  1987,  28:  4733 
• 19 Gosselin F. O’Shea PD. Roy S. Reamer RA. Chen C. Volante RP. Org. Lett.  2005,  7:  355 

17

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.

18

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.