Langlois Reagent Mediated Tandem Cyclization of o-Hydroxyaryl Enaminones for the Synthesis of 3-(Trifluoromethyl)chromones

Abstract

An efficient and simple synthesis of various 3-(trifluoromethyl)chromones from enamino ketones is described. The key step in the synthesis involves the introduction of a trifluoromethyl (CF₃) moiety onto a chromone structure. The significant features of this method include simple operational procedures, the high purity and yield of the product, and excellent regioselectivity.

Key words

trifluoromethylation - Langlois reagent - enamino ketones - trifluoromethylchromones - copper acetate

Publication History

Received: 20 April 2022

Accepted after revision: 21 July 2022

Accepted Manuscript online:
21 July 2022

Article published online:
24 August 2022

• References and Notes

• 1 Tredwell M, Gouverneur V. Angew. Chem. Int. Ed. 2012; 51: 11426
• 2 Reis J, Gaspar A, Milhazes N, Borges M. J. Med. Chem. 2017; 60: 7941
• 3 Leahy JJ. J, Golding BT, Griffin RJ, Hardcastle IR, Richardson C, Rigoreau L, Smith GC. M. Bioorg. Med. Chem. Lett. 2004; 14: 6083
• 4a Griffin RJ, Fontana G, Golding BT, Guiard S, Hardcastle IR, Leahy JJ. J, Martin N, Richardson C, Rigoreau L, Stockley M, Smith GC. M. J. Med. Chem. 2005; 48: 569
• 4b Kim HP, Son KH, Chang HW, Kang SS. J. Pharmacol. Sci. (Amsterdam, Neth.) 2004; 96: 229
• 5 Bhat AS, Whetstone JL, Brueggemeier R. Tetrahedron Lett. 1999; 40: 2469
• 6a Bennett CJ, Caldwell ST, McPhail DB, Morrice PC, Duthie GG, Hartley RC. Bioorg. Med. Chem. 2004; 12: 2079
• 6b Krishnamachari V, Levin LH, Zhou C, Paré PW. Chem. Res. Toxicol. 2004; 17: 795
• 7 Marder M, Viola H, Bacigaluppo JA, Colombo MI, Wasowski C, Wolfman C, Medina V, Rúveda V, Paladini AC. Biochem. Biophys. Res. Commun. 1998; 249: 481
• 8 Hoult JR. S, Moroney MA, Payá M. Methods Enzymol. 1994; 234: 443
• 9 Parmar VS, Bracke ME, Philippe J, Wengel J, Jain SC, Olsen CE, Bisht KS, Sharma NK, Courtens A, Sharma SK, Venneken K, Van Marck V, Singh SK, Kumar N, Kumar A, Malhothra S, Kumar R, Rajwanshi VK, Jain R, Maree MM. Bioorg. Med. Chem. 1997; 5: 1609
• 10 Galietta LJ, Springsteel MF, Eda M, Neidzinsk EJ, By K, Haddadin MJ, Nantz MH, Verkman AS. J. Biol. Chem. 2001; 276: 19723
• 11a Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
• 11b Gaspar A, Matos JM, Garrideo J, Uriarte E, Borges F. Chem. Rev. 2014; 114: 4960
• 12a Lewinsohn E, Britsch L, Mazur Y, Gressel J. Plant Physiol. 1989; 91: 1323
• 12b Langer P. Synlett 2022; 33: 207
• 13a Kirk KL. Org. Process Res. Dev. 2008; 12: 305
• 13b Smart BE. J. Fluorine Chem. 2001; 109: 3
• 13c Thomas CJ. Curr. Top. Med. Chem. (Sharjah, United Arab Emirates) 2006; 6: 1529
• 14 Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 15 Wang R, Han J, Li C, Zhang J, Liang Y, Wang T, Zhang Z. Org. Biomol. Chem. 2018; 16: 2479
• 16a Yoder NC, Kumar K. Chem. Soc. Rev. 2002; 31: 335
• 16b Truong T, Klimovica K, Daugulis O. J. Am. Chem. Soc. 2013; 135: 9342
• 16c Merino E, Nevado C. Chem. Soc. Rev. 2014; 43: 6598
• 16d Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683
• 17a Kees K, Fitzgerald JJ. Jr, Steiner KE, Mattes JF, Mihan B, Tosi T, Mondoro D, McCaleb ML. J. Med. Chem. 1996; 39: 3920
• 17b Navarrete-Vázquez C, Cedillo R, Hernández-Campos A, Yépez L, Hernández-Luis F, Valdez J, Morales R, Cortés R, Hernández M, Castillo R. Bioorg. Med. Chem. Lett. 2001; 11: 187
• 17c Deng Y, Sun C, Hunt DK, Chen C.-L, Grossman TH, Sutcliffe JA, Xiao X.-Y. J. Med. Chem. 2017; 60: 2498
• 17d Maschke M, Alborzinia H, Lieb M, Wölfi S, Metzler-Nolte N. ChemMedChem 2014; 9: 1188

For selected references, see:
• 18a Tomashenko OA, Grushin VV. Chem. Rev. 2011; 111: 4475
• 18b Ma J.-A, Cahard D. Chem. Rev. 2004; 104: 6119
• 18c Xu X.-H, Matsuzaki K, Shibata N. Chem. Rev. 2015; 115: 731
• 18d Qing F. Youji Huaxue 2012; 32: 815
• 18e Zhang C. Adv. Synth. Catal. 2017; 359: 372
• 18f Pan X, Xia H, Wu J. Org. Chem. Front. 2016; 3: 1163
• 18g Wu X.-F, Neumann H, Beller M. Chem. Asian J. 2012; 7: 1744
• 18h Studer A. Angew. Chem. Int. Ed. 2012; 51: 8950
• 18i Zhang C. Adv. Synth. Catal. 2014; 356: 2895
• 18j Wei Q, Chen J.-R, Hu X.-Q, Yang X.-C, Lu B, Xiao W.-J. Org. Lett. 2015; 17: 4464
• 18k Shang SJ, Liu D, Liu Z.-Q. Org. Chem. Front. 2018; 5: 2856
• 19 Nagib DA, MacMillan DW. C. Nature 2011; 480: 224
• 20 Fang Z, Ning Y, Mi P, Liao P, Bi X. Org. Lett. 2014; 16: 1522
• 21 Xiang H, Zhao Q, Tang Z, Xiao J, Xia P, Wang C, Yang C, Chen X, Yang H. Org. Lett. 2017; 19: 146
• 22 Yu Q, Liu Y, Wan J.-P. Org. Chem. Front. 2020; 7: 2770
• 23a Zhou X, He X, Hua Y, Yan P, Li Y. CN 112079805, 2020
• 23b Tan Z, Zhang S, Zhang Y, Li Y, Ni M, Feng B. J. Org. Chem. 2017; 82: 9384
• 23c Huang B, Bu X.-S, Xu J, Dai J.-J, Feng Y.-S, Xu H.-J. Asian J. Org. Chem. 2018; 7: 137
• 23d Mehta J, Aryal P, Reddy VP. Eur. J. Org. Chem. 2021; 2018
• 24 Ji Y, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. PNAS 2011; 108: 14411
• 25a Sambaiah M, Ragavulu K, Kumar KS, Yannam S, Behera M. New J. Chem. 2017; 41: 10020
• 25b Balakrishna C, Gudipati R, Kandula V, Yannam S, Devi PU, Behera M. New J. Chem. 2019; 43: 2458
• 25c Balakrishna C, Kandula V, Gudipati R, Yannam S, Devi PU, Behera M. Synlett 2018; 29: 1087
• 25d Kandula V, Balakrishna C, Behera M, Nagababu U, Kumar GK, Chatterjee A. ChemistrySelect 2019; 4: 14043
• 25e Kandula V, Gudipati R, Chatterjee A, Kaliyaperumala M, Yannam S, Behera M. J. Chem. Sci. 2017; 129: 1233
• 25f Balakrishna C, Nagaraju P, Satyanarayana Y, Devi PU, Behera M. Bioorg. Med. Chem. Lett. 2015; 125: 4753
• 26 Kandula V, Thota PK, Mallesham P, Ragavulu K, Chatterjee A, Yannam S, Behera M. Synlett 2019; 30: 2295
• 27 3-(Trifluoromethyl)chromone (5a): Typical Procedure CF₃SO₂Na (326 mg, 2.094 mmol), TBHP (283 mg, 3.14 mmol), and Cu(OAc)₂ (9 mg, 0.052 mmol) were added sequentially to a stirred solution of enaminone 4a (200 mg, 1.047 mmol) in DMSO (5 mL), and the mixture was stirred at RT for 16 h. When the reaction was complete (TLC), the mixture was diluted with EtOAc and washed with H₂O. The organic layer was separated and concentrated, and the crude product was purified by column chromatography (silica gel, EtOAc–hexane) to give an off-white solid; yield: 174 mg (77%); mp 99–102 °C. FTIR (KBr): 3084, 1658, 1465, 1398, 1350, 1267, 1122, 848, 756 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 9.01 (d, J = 0.8 Hz, 1 H), 8.13 (dd, J = 1.6, 8 Hz, 1 H), 7.39–7.896 (m, 1 H), 7.78 (d, J = 8.4 Hz, 1 H), 7.62–7.58 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 172.79, 155.99, 155.78, 155.71, 134.81, 126.45, 126.18, 123.505, 120.800 (q, J = 270.2 Hz, CF₃), 118.29. ¹⁹F NMR (CDCl₃): δ = –62.76 (s, CF₃). MS (EI): m/z (%) = 214 (100) [M + H]⁺. HRMS: (ESI): m/z [M + H]⁺calcd for C₁₀H₆F₃O₂: 215.0320; found: 215.2598.