One-Pot Synthesis of α-Fluoroketones and 3-Fluoro-2,4-diaryl­furans from Trifluoromethyl β-Diketones via Decarboxylation

Abstract

A facile and mild one-pot protocol via decarboxylation of trifluoromethyl β-diketones has been developed for the construction of α-fluoroketones and 3-fluoro-2,4-diarylfurans which are important units in many biologically active compounds and useful precursors in a variety of functional-group transformations.

Key words

fluorine - α-fluoroketones - 3-fluorofurans - one-pot - decarboxylation

• References and Notes

• 1a Jeschke P. Science 2010; 66: 10
• 1b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
• 1c Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 1d Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 1e Chambers RD. Fluorine in Organic Chemistry . Blackwell Publishing; Oxford: 2004
• 1f Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. Wiley-Blackwell; Oxford: 2009
• 2 Ilardi EA, Vitaku E, Njardarson JT. J. Med. Chem. 2014; 57: 2832
• 3a Thvedt TH. K, Fuglseth E, Sundby E, Hoff BH. Tetrahedron 2010; 66: 6733
• 3b Malamakal RM, Hess WR, Davis TA. Org. Lett. 2010; 12: 2186
• 4a Borzecka W, Lavandera I, Gotor V. J. Org. Chem. 2013; 78: 7312
• 4b Fuglseth E, Sundby E, Hoff BH. J. Fluorine Chem. 2009; 130: 600
• 4c Mohanta PK, Davis TA, Gooch JR, Flowers RA. J. Am. Chem. Soc. 2005; 127: 11896
• 4d Matsuda T, Harada T, Nakamura K. Chem. Commun. 2000; 1367
• 5a He Y, Zhang X, Shen N, Fan X. J. Fluorine Chem. 2013; 156: 9
• 5b Lawrence NJ, Patterson RP, Ooi LL, Cook D, Ducki S. Bioorg. Med. Chem. Lett. 2006; 16: 5844
• 5c Heinrich MR. Tetrahedron Lett. 2007; 48: 3895
• 6 Furuya T, Kuttruff CA, Ritter T. Curr. Opin. Drug Discovery Dev. 2008; 11: 803
• 7a Liu J, Chan J, Bryant CM, Duspara PA, Lee EE, Powell D, Yang H, Liu Z, Walpole C, Roberts E, Batey RA. Tetrahedron Lett. 2012; 53: 2971
• 7b Yi WB, Huang X, Cai C, Zhang W. Green Chem. 2012; 14: 3185
• 7c Kwiatkowski P, Beeson TD, Conrad JC, MacMillan DW. C. J. Am. Chem. Soc. 2011; 133: 1738
• 7d Ahlsten N, Bartoszewicz A, Agrawal S, Martín-Matute B. Synthesis 2011; 2600
• 7e Fuglseth E, Thvedt TH. K, Møll MF, Hoff BH. Tetrahedron 2008; 64: 7318
• 7f Stavber S, Jereb M, Zupan M. Chem. Commun. 2000; 1323
• 7g Peng W, Shreeve JM. J. Org. Chem. 2005; 70: 5760
• 7h Thvedt TH. K, Fuglseth E, Sundby E, Hoff BH. Tetrahedron 2009; 65: 9550
• 7i Stavber G, Zupan M, Stavber S. Synlett 2009; 589
• 8a He Y, Zhang X, Shen N, Fan X. J. Fluorine Chem. 2013; 156: 9
• 8b Chen ZZ, Zhu W, Zheng ZB, Zou XZ. J. Fluorine Chem. 2010; 131: 340
• 8c Makosza M, Bujok R. Tetrahedron Lett. 2004; 45: 1385
• 8d Kim DW, Song CE, Chi DY. J. Am. Chem. Soc. 2002; 124: 10278
• 8e Wagner PJ, Thomas MJ, Puchalski AE. J. Am. Chem. Soc. 1986; 108: 7739
• 8f Liotta CL, Harris HP. J. Am. Chem. Soc. 1974; 96: 2250
• 8g Fitjer L. Synthesis 1977; 189
• 8h Leroy J. J. Org. Chem. 1981; 46: 206
• 9a Lipshutz BH. Chem. Rev. 1986; 86: 795
• 9b Dean FM In Advances in Heterocyclic Chemistry . Vol. 31. Katritzky AR. Academic Press; New York: 1983: 273
• 9c Natural Products Chemistry. Vol. 1–3. Nakanishi K, Goto T, Ito S, Natori S, Nozoe S. Kodansha; Tokyo: 1974
• 10a Paal C. Ber. Dtsch. Chem. Ges. 1884; 17: 2756
• 10b Knorr L. Ber. Dtsch. Chem. Ges. 1884; 17: 2863
• 11a Feist F. Ber. Dtsch. Chem. Ges. 1902; 35: 1545
• 11b Benary E. Ber. Dtsch. Chem. Ges. 1911; 44: 489
• 12 Ma YH, Zhang S, Yang SP, Song FJ, You JS. Angew. Chem. Int. Ed. 2014; 53: 7870
• 13 Bronnert DL. E, Saunders BC. Tetrahedron 1965; 21: 3325
• 14 Arimitsu S, Jacobsen JM, Hammond GB. J. Org. Chem. 2008; 73: 2886
• 15a Saidalium I, Fang X, Lv WW, Yang XY, He XP, Zhang JY, Wu FH. Adv. Synth. Catal. 2013; 355: 857
• 15b Saidalium I, Fang X, He XP, Liang J, Yang XY, Wu FH. Angew. Chem. Int. Ed. 2013; 52: 5566
• 16a Sloop JC, Boyle PD, Fountain AW, Pearman WF, Swann JA. Eur. J. Org. Chem. 2011; 936
• 16b Sloop JC, Bumgardner CL, Washington G, Loehle WD, Sankar SS, Lewis AB. J. Fluorine Chem. 2006; 127: 780
• 17 Typical Experimental Procedure for the Synthesis of 2 from 1 To a mixture of 1d (146 mg, 0.5 mmol) and Na₂CO₃ (159 mg, 1.5 mmol) in MeCN (0.3 mL) and H₂O (0.1 mL), a solution of Selectfluor (212 mg, 0.6 mmol) in MeCN (0.3 mL) and H₂O (0.3 mL) was added over 30 min at 0 °C. The reaction mixture was then stirred for 8 h at 0 °C. When the reaction was complete (monitored by TLC), sat. aq NH₄Cl (4 mL) was added to quench the reaction. After extraction with CH₂Cl₂ and drying with Na₂SO₄, the organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel using hexane–EtOAc (20:1) as eluent to afford the desired products 2d (64 mg, 60%). 1-[(1,1′-Biphenyl)-4-yl]-2-fluoroethanone (2d) White solid; mp 131.5–132.4 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.73–7.71 (m, 2 H), 7.64–7.62 (m, 2 H), 7.51–7.47 (m, 2 H), 7.44–7.40 (m, 1 H), 5.56 (d, J = 48.0 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 193.0 (d, J = 15.2 Hz), 146.8, 139.5, 132.3, 129.0, 128.5, 128.4 (d, J = 2.0 Hz), 127.4, 127.2, 83.7 (d, J = 183.8 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –230.28 (t, J = 48.8 Hz, 1 F). IR (KBr): ν = 3380, 2929, 2851, 1700, 1602, 1407, 1241, 1207, 1091, 975, 766, 691 cm^–1. MS (EI): m/z = 214, 182, 181 (100), 152, 76, 51. HRMS: m/z calcd for [C₁₄H₁₁FO]⁺: 214.0794; found: 214.0795.
• 18 Typical Experimental Procedure for the Synthesis of 3 from 1 To a mixture of 1a (108 mg, 0.5 mmol) and NaOH (80 mg, 2.0 mmol) in MeCN (0.2 mL) and H₂O (0.1 mL), a solution of Selectfluor (212 mg, 0.6 mmol) in MeCN (0.3 mL) and H₂O (0.1 mL) was added slowly at 0 °C. The reaction mixture was stirred for 3 h at 0 °C. It was then heated for 6 h at 50 °C. When the reaction was complete (monitored by TLC), sat. aq NH₄Cl (6 mL) was added to quench the reaction. After extraction with EtOAc and drying with Na₂SO₄, the organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel using hexane–EtOAc (60:1 to 30:1) as eluent to afford the desired products 3a (40 mg, 67%). 3-Fluoro-2,4-diphenylfuran (3a) White solid; mp 78.4–79.0 °C. ¹H NMR (400 MHz, CDCl₃) δ = 7.75 (d, J = 8.0 Hz, 2 H), 7.60 (d, J = 8.0 Hz, 2 H), 7.54 (d, J = 4.0 Hz, 1 H), 7.46–7.41 (m, 4 H), 7.36–7.29 (m, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 147.5 (d, J = 256.5 Hz), 137.7 (d, J = 21.2 Hz), 136.3 (d, J = 7.1 Hz), 129.3 (d, J = 3.0 Hz), 128.9 (d, J = 3.0 Hz), 128.8, 128.7, 127.7, 127.3, 126.5 (d, J = 3.0 Hz), 123.5 (d, J = 6.0 Hz), 119.4 (d, J = 14.1 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –166.91 (d, J = 3.7 Hz, 1 F). IR (KBr): ν = 3422, 3151, 2923, 2852, 1948, 1879, 1634, 1496, 1443, 1410, 1066, 908, 759, 747, 690 cm^–1. MS (EI): m/z = 238 (100), 209, 133, 105, 91, 77, 44. HRMS: m/z calcd for [C₁₆H₁₁FO]⁺: 238.0794; found: 238.0795.