Copper-Catalyzed Aerobic C–H Trifluoromethylation of Phenanthrolines

Abstract

Direct C–H trifluoromethylation of heterocycles is a valuable transformation. In particular, nonprecious metal-catalyzed C–H trifluoromethylation processes, which do not proceed through CF₃ radical species, have been less developed. In this cluster report, a new copper-catalyzed aerobic C–H trifluoromethylation of phenanthrolines is described. This transformation affords trifluoromethylated phenanthrolines that have not been synthesized and preliminary mechanistic studies suggest that the CF₃ group transfer may occur through cooperative activation.

Key words

copper - fluorine - oxygen - oxidation - heterocycles

• References and Notes

• 1 These two authors contributed equally.
• 2a Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 2b Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320

For selected examples of transition-metal-catalyzed trifluromethyaltion of aromatics and related compounds, see:
• 3a Chen Q.-Y, Wu S.-W. J. Chem. Soc., Chem. Commun. 1989; 705
• 3b Oishi M, Kondo H, Amii H. Chem. Commun. 2009; 1909
• 3c Cho EJ, Senecal TD, Kinzel T, Zhang Y, Watson DA, Buchwald SL. Science 2010; 328: 1679
• 3d Teverovskiy G, Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 7312
• 3e Parsons AT, Senecal TD, Buchwald SL. Angew. Chem. Int. Ed. 2012; 51: 2947
• 3f Dubinina GG, Furutachi H, Vicic DA. J. Am. Chem. Soc. 2008; 130: 8600
• 3g Zanardi A, Novikov MA, Martin E, Benet-Buchholz J, Grushin VV. J. Am. Chem. Soc. 2011; 133: 20901
• 3h Tomashenko OA, Escudero-Adán EC, Martínez Belmonte M, Grushin VV. Angew. Chem. Int. Ed. 2011; 50: 7655
• 3i Morimoto H, Tsubogo T, Litvinas ND, Hartwig JF. Angew. Chem. Int. Ed. 2011; 50: 3793
• 3j Kawai H, Furukawa T, Nomura Y, Tokunaga E, Shibata N. Org. Lett. 2011; 13: 3596
• 3k Knauber T, Arikan F, Röschenthaler G.-V, Gooßen LJ. Chem. Eur. J. 2011; 17: 2689
• 3l Hafner A, Bräse S. Angew. Chem. Int. Ed. 2012; 51: 3713
• 3m Qi Q, Shen Q, Lu L. J. Am. Chem. Soc. 2012; 134: 6548
• 3n Shimizu R, Egami H, Nagi T, Chae J, Hamashima Y, Sodeoka M. Tetrahedron Lett. 2010; 51: 5947
• 3o He Z, Luo T, Hu M, Cao Y, Hu J. Angew. Chem. Int. Ed. 2012; 51: 3944
• 3p Liu L.-P, Xu B, Mashuta MS, Hammond GB. J. Am. Chem. Soc. 2008; 130: 17642
• 3q Morandi B, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 938
• 4a Nagib DA, MacMillan DW. C. Nature (London, U.K.) 2011; 480: 224
• 4b Ji Y, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 14411
• 4c Fujiwara Y, Dixon JA, O’Hara F, Funder ED, Dixon DD, Rodriguez RA, Baxter RD, Herle B, Sach N, Collins MR, Ishihara Y, Baran PS. Nature (London, U.K.) 2012; 492: 95
• 4d Ye Y, Sanford MS. J. Am. Chem. Soc. 2012; 134: 9034
• 5a Wang X, Truesdale L, Yu J.-Q. J. Am. Chem. Soc. 2010; 132: 3648
• 5b Ball ND, Kampf JW, Sanford MS. J. Am. Chem. Soc. 2010; 132: 2878
• 5c Ball ND, Gary JB, Ye Y, Sanford MS. J. Am. Chem. Soc. 2011; 133: 7577
• 5d Mu X, Wu T, Wang H.-Y, Guo Y.-L, Liu G. J. Am. Chem. Soc. 2012; 134: 878
• 6 Chu L, Qing F.-L. J. Am. Chem. Soc. 2012; 134: 1298
• 7 For a selected example of functionalized phenanthrolines as ligands in catalysis, see: Altman RA, Buchwald SL. Org. Lett. 2006; 8: 2779 ; a thorough search of REAXYS^® database revealed that trifluoromethylated phenanthrolines have not been reported
• 8 Amii, Qing, and Hartwig have each developed arene trifluoromethylation methods with the copper(I)/1 complex. See ref. 3b,i, 6.
• 9 A closely related example is the commercially available dichloro(1,10-phenanthroline) copper(II).
• 10 For an example of nucleophilic addition to the C=N bond of 1,10-phenanthroline, see: Nishikawa Y, Yamamoto H. J. Am. Chem. Soc. 2011; 133: 8432

For relevant studies in this group, see:
• 11a Lu D.-F, Zhu C.-L, Xu H. Chem. Sci. 2013; 4: 2478
• 11b Zhang Y.-Q, Liu J.-D, Xu H. Org. Biomol. Chem. 2013; 11: 6242
• 12 Schönecker B, Zheldakova T, Liu Y, Kötteritzsch M, Günther W, Görls H. Angew. Chem. Int. Ed. 2003; 42: 3240
• 13 Typical Experimental Procedure To a mixture of 1,10-phenanthroline (1, 36 mg, 0.2 mmol), Cu(OAc)₂ (7.4 mg, 0.04 mmol), KOAc (9.8 mg, 0.1 mmol), and AcOH (6.0 μL, 0.1 mmol) in toluene (4.0 mL), TMSCF₃ (30 μL, 0.2 mmol) was added at room temperature under an O₂ atmosphere. The reaction mixture was stirred at 40 °C for 3 h. Another portion of TMSCF₃ (30 μL, 0.2 mmol) was added, and stirring was continued at 40 °C. The reaction was monitored by TLC. After the starting material was completely consumed, the reaction was quenched by H₂O and extracted with EtOAc (3 × 4 mL). The combined organic layer was washed by brine, dried over Na₂SO₄, and concentrated in vacuo. The product 2 was isolated through a silica gel flash column (40% EtOAc in hexanes) as a white foam (41 mg, 80% yield). 2-(Trifluoromethyl)-1,10-phenanthroline (2) ¹H NMR (400 MHz, CDCl₃): δ = 9.24 (s, H_a), 8.38 (d, J = 8.4 Hz, H_f), 8.23 (d, J = 8.6 Hz, H_c), 7.93 (d, J = 8.4 Hz, H_g), 7.85, 7.78 (d, J = 8.8Hz, H_d and H_e), 7.65 (m, H_b) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 151.06, 147.7 (q, J = 35.0 Hz), 145.72, 145.56, 137.83, 136.09, 129.76, 129.10, 128.79, 125.70, 123.59, 124.30 (q, J = 273 Hz), 119.00 ppm. ¹⁹F NMR (377 MHz, CDCl₃): δ = –66.59 (s, 3 F) ppm. IR (neat): ν_max = 3696, 2967, 2217, 1595, 1337, 1112, 851, 746 cm^–1. ESI-HRMS: m/z calcd for C₁₃H₈N₂F₃ ⁺ [M + H⁺]: 249.0640; found: 249.0642.