A Practical Method for Metal-Free Radical Trifluoromethylation of Styrenes with NaSO₂CF₃

Abstract

A mild and practical protocol for the metal-free trifluoromethylation of styrenes using NaSO₂CF₃ (Langlois reagent) and TBHP was developed. The approach provides efficient access to α-trifluoromethylated ketones and alcohols in moderate to good yields.

Key words

metal-free - trifluoromethylation - ketones - alcohols - Langlois reagent - styrenes

• References and notes

• 1a Banks RE. Organofluorine Chemicals and their Industrial Applications. Ellis Horwood; West Sussex: 1979
• 1b Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
• 1c Muller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 1d Hird M. Chem. Soc. Rev. 2007; 36: 2070
• 1e Kirk KL. Org. Process Res. Dev. 2008; 12: 305
• 2a For an important early review on the subject, see: Welch JT. Tetrahedron 1987; 43: 3123
• 2b Special Issue on ‘Fluorine in the Life Sciences’: ChemBioChem 2004; 5: 557
• 2c Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 3a Litvinas ND, Fier PS, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 536
• 3b Cho EJ, Senecal TD, Kinzel T, Zhang Y, Watson DA, Buchwald SL. Science 2010; 328: 1679
• 3c Morimoto H, Tsubogo T, Litvinas ND, Hartwig JF. Angew. Chem. Int. Ed. 2011; 50: 3793
• 4a 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 2012; 492: 95
• 4b Ji YN, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 14411
• 5a Novák P, Lishchynskyi A, Grushin VV. Angew. Chem. Int. Ed. 2012; 51: 7767
• 5b Wang X, Xu Y, Mo F, Ji G, Qiu D, Feng J, Ye Y, Zhang S, Zhang Y, Wang J. J. Am. Chem. Soc. 2013; 135: 10300
• 6a Xu J, Luo D.-F, Xiao B, Liu Z.-J, Gong T.-J, Fu Y, Liu L. Chem. Commun. 2011; 47: 4300
• 6b Studer A. Angew. Chem. Int. Ed. 2012; 51: 8950
• 7a Liu T, Shen Q. Org. Lett. 2011; 13: 2342
• 7b Liu T, Shao X, Wu Y, Shen Q. Angew. Chem. Int. Ed. 2012; 51: 540
• 7c Feng C, Loh T.-P. Chem. Sci. 2012; 3: 3458
• 7d Dai J.-J, Fang C, Xiao B, Yi J, Xu J, Liu Z.-J, Lu X, Liu L, Fu Y. J. Am. Chem. Soc. 2013; 135: 8436
• 8a Ye Y, Sanford MS. J. Am. Chem. Soc. 2012; 134: 9034
• 8b Nagib DA, MacMillan DW. C. Nature 2011; 480: 224
• 8c Qi Q, Shen Q, Lu L. J. Am. Chem. Soc. 2012; 134: 6548
• 9a Cahard D, Ma J.-A. Chem. Rev. 2004; 104: 6119
• 9b Itoh Y, Mikami Y. Org. Lett. 2005; 7: 649
• 9c Kieltsch I, Eisenberger P, Stanek K, Togni A. Chimia 2008; 62: 260
• 9d Uneyama K, Katagiri T, Amii H. Acc. Chem. Res. 2008; 41: 817
• 9e Matousek V, Togni A, Bizet V, Cahard D. Org. Lett. 2011; 13: 5762
• 9f Pham PV, Nagib DA, MacMillan DW. C. Angew. Chem. Int. Ed. 2011; 50: 6119
• 9g Umemoto T, Ishihara S. J. Am. Chem. Soc. 1993; 115: 2156
• 10a Novák P, Lishchynskyi A, Grushin VV. J. Am. Chem. Soc. 2012; 134: 16167
• 10b Zanardi A, Novikov MA, Martin E, Benet-Buchholz J, Grushin VV. J. Am. Chem. Soc. 2011; 133: 20901
• 11 He Z, Zhang R, Hu M, Li L, Ni C, Hu J. Chem. Sci. 2013; 4: 3478
• 12 While this manuscript was in preparation, a silver-catalyzed oxidative trifluoromethylation of unactivated olefins was reported, see: Deb A, Manna S, Modak A, Patra T, Maity S, Maiti D. Angew. Chem. Int. Ed. 2013; 52: 9747
• 13a Zhang CP, Wang ZL, Chen QY, Zhang CT, Gu YC, Xiao JC. Chem. Commun. 2011; 47: 6632
• 13b Wilger DJ, Gesmundo NJ, Nicewicz DA. Chem. Sci. 2013; 4: 3160
• 14a Langlois BR, Laurent E, Roidot N. Tetrahedron Lett. 1991; 32: 7525
• 14b Langlois BR, Laurent E, Roidot N. Tetrahedron Lett. 1992; 33: 1291
• 15a Ye Y, Künzi SA, Sanford MS. Org. Lett. 2012; 14: 4979
• 15b Yang Y.-D, Iwamoto K, Tokunaga E, Shibata N. Chem. Commun. 2013; 49: 5510
• 16a Li Z, Cui Z, Liu Z.-Q. Org. Lett. 2013; 15: 406
• 16b Lu Q, Liu C, Peng P, Liu Z, Fu L, Huang J, Lei A. Asian J. Org. Chem. 2014; 3: 273
• 17 Typical Procedure: To a septum-capped 25 mL sealed tube with a magnetic stirring bar were added CF₃SO₂Na (1.8 mmol) and BQ (0.3 mmol) in MeCN–H₂O (4:1; 4 mL) under O₂, followed by the addition of styrene 1a (0.3 mmol) and tBuOOH (2.4 mmol). The sealed tube was screw capped and heated at 80 °C for 16–24 h (oil bath). Upon completion, the mixture was cooled to room temperature and diluted with H₂O (10 mL). The aqueous layer was extracted with EtOAc (3 × 10 mL) and the combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (hexane) to provide pure products 2a and 3a in 57% combined yield. Purification by flash column chromatography on silica gel (hexanes–EtOAc, 20:1 v/v) gave the pure products. Compound 2a: Yield: 36%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 7.4 Hz, 2 H), 7.57 (t, J = 7.4 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 2 H), 3.73 (q, J = 10.0 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 189.7 (q, J = 2.8 Hz), 135.7, 134.1, 128.9, 128.3, 124.0 (q, J = 276.7 Hz), 41.9 (q, J = 28.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –62.1 (t, J = 10.0 Hz, 3F). Compound 3a: Yield: 21%; colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.41 (m, 5 H), 7.08 (dd, J = 9.0, 3.6 Hz, 1 H), 2.56–2.70 (m, 1 H), 2.39–2.52 (m, 1 H), 2.25 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 142, 128.9, 128.4, 125.9 (q, J = 275.7 Hz), 125.7, 68.8 (d, J = 3.3 Hz), 42.9 (q, J = 26.9 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –63.7 (t, J = 10.5 Hz, 3F). HRMS (EI): m/z [M + H]⁺ calcd. for C₉H₁₀F₃O: 191.0684; found: 191.0688.