Synthesis of CF₃-Containing 1,2,3,4-Tetrahydroisoquinoline-3-Phosphonates via Regioselective Ruthenium-Catalyzed Co-cyclotrimerization of 1,7-Aza­diynes

Abstract

An efficient access to novel trifluoromethyl-substituted phosphonate analogues of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (TIC) derivatives based on regioselective ruthenium-­catalyzed co-cyclotrimerization of functionalized 1,7-diynes with various alkynes has been developed using RuClCp*cod and pre­ferably Grubbs second-generation catalysts.

Key words

α-aminophosphonates - 1,7-azadiynes - alkynes - ­cyclo­trimerization - ruthenium catalysis

• References and Notes

• 1a Aminophosphonic and Aminophosphinic Acids – Chemistry and Biological Activity. Kuhkhar VP, Hudson HR. Wiley; Chichester: 2000
• 1b Ordonez M, Sayago FJ, Cativiela C. Tetrahedron 2012; 68: 6369
• 2a Troev KD. Chemistry and Application of H-Phosphonates. Elsevier; Amsterdam: 2006
• 2b Naydenova ED, Todorov PT, Troev KD. Amino Acids 2010; 38: 23
• 3a Kafarski P, Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem. 1991; 63: 193
• 3b Hiratake J, Oda J. Biosci. Biotechnol. Biochem. 1997; 61: 211
• 3c Alonso E, Solis A, del Pozo C. Synlett 2000; 698
• 3d Kafarski P, Lejczak B. Curr. Med. Chem. 2001; 1: 301
• 4 Smith AB. III, Yager KM, Taylor CM. J. Am. Chem. Soc. 1995; 117: 10879
• 5 Hirschmann R, Smith AB. III, Taylor CM, Benkovic PA, Taylor SD, Yager KM, Sprengeler PA, Benkovic SJ. Science 1994; 265: 234
• 6a Allen JG, Atherton FR, Hall MJ, Hassal CH, Holmes SW, Lambert RW, Nisbet LJ, Ringrose PS. Nature (London) 1978; 272: 56
• 6b Atherton FR, Hassall CH, Lambert RW. J. Med. Chem. 1986; 29: 29
• 7 Reddy SS, Sankar AU. R, Raju CN, Rao VK. S. Afr. J. Chem. 2008; 61: 97
• 8 Maier L, Diel PJ. Phosphorus Sulfur Silicon Relat. Elem. 1991; 57: 57
• 9 Gavras I, Vlahakos D, Melby JC, Gavras H. J. Clin. Pharm. 1984; 24: 343
• 10 Asaoka T, Yazawa K, Mikami Y, Takahashi K. J. Antibiot. 1982; 35: 1708
• 11 Francois G, Bringmann G, Phillipson JD, Boyd MR, Assi LA, Schneider C, Timperman G. US 5,639,761, 1994
• 12a Otake K, Azukizawa S, Fukui M, Kunishiro K, Kamemoto H, Kanda M, Miike T, Kasai M, Shirahase H. Bioorg. Med. Chem. 2012; 20: 1060
• 12b Vendeville S, Goossens F, Debreu-Fontaine MA, Landry V, Davioud-Charvet E, Grellier P, Scharpe S, Sergheraert G. Bioorg. Med. Chem. 2002; 10: 1719
• 12c Matter H, Schudok M, Schwab W, Thorwart W, Barbier D, Billen G, Haase B, Neises B, Weithmann KU, Wollmann T. Bioorg. Med. Chem. 2002; 10: 3529
• 12d Zhang Y, Feng J, Jia Y, Wang X, Zhang L, Liu C, Fang H, Xu W. J. Med. Chem. 2011; 54: 2823
• 13 Wang A, U’Prichard DC, Marder VJ. US 0061885 A1, 2002
• 14a Balboni G, Fiorini S, Baldisserotto A, Trapella C, Sasaki Y, Ambo A, Marczak ED, Lazarus LH, Salvadori S. J. Med. Chem. 2008; 51: 5109
• 14b Ballet S, Feytens D, De Wachter R, De Vlaeminck M, Marczak ED, Salvadori S, de Graaf C, Rognan D, Negri L, Lattanzi R, Lazarus LH, Tourwé D, Balboni G. Bioorg. Med. Chem. Lett. 2009; 19: 433
• 15 Markina NA, Mancuso R, Neuenswander B, Lushington GH, Larock RC. ACS Comb. Sci. 2011; 13: 265
• 16a Kirsch P. Modern Fluoroorganic Chemistry . Wiley-VCH; Weinheim: 2004
• 16b Uneyama K. Organofluorine Chemistry . Blackwell; Oxford: 2006
• 16c Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
• 16d Schlosser M. Angew. Chem. Int. Ed. 2006; 45: 5432
• 16e Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 16f Hird M. Chem. Soc. Rev. 2007; 36: 2070
• 16g Kirk KL. Org. Process Res. Dev. 2008; 12: 305
• 16h O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
• 17a Lundgren RJ, Stradiotto M. Angew. Chem. Int. Ed. 2010; 49: 9322
• 17b Nie J, Guo H.-C, Cahard D, Ma J.-A. Chem. Rev. 2011; 111: 455
• 18 Shchetnikov GT, Osipov SN, Bruneau C, Dixneuf PH. Synlett 2008; 578
• 19 Zotova MA, Vasilyeva TP, Peregudov AS, Osipov SN. J. Fluorine Chem. 2012; 135: 33

Related access to nonfluorinated TIC-derivatives:
• 20a Kotha S, Sreenivasachary N. Eur. J. Org. Chem. 2001; 3375
• 20b Kotha S, Banerjee S. Synthesis 2007; 1015

Selected papers on Ru-catalyzed alkyne cyclotrimerization:
• 21a Yamamoto Y, Kitahara H, Ogawa R, Itoh K. J. Org. Chem. 1998; 63: 9610
• 21b Yamamoto Y, Ogawa R, Itoh K. Chem. Commun. 2000; 549
• 21c Yamamoto Y, Arakawa T, Ogawa R, Itoh K. J. Am. Chem. Soc. 2003; 125: 12143
• 21d Saito S, Yamamoto Y. Chem. Rev. 2000; 100: 2901
• 22a Kirchner K, Calhorda MJ, Schmid R, Veiros LF. J. Am. Chem. Soc. 2003; 125: 11721
• 22b Paih JL, Monnier F, Dérien S, Dixneuf PH, Clot E, Eisenstein O. J. Am. Chem. Soc. 2003; 125: 11964
• 22c Le Paih J, Dérien S, Demerseman B, Bruneau C, Dixneuf PH, Toupet L, Dazinger G, Kirchner K. Chem. Eur. J. 2005; 11: 1312
• 23a Peters J.-U, Blechert S. Chem. Commun. 1997; 1983
• 23b Witulski B, Stengel T, Fernández-Hernández JM. Chem. Commun. 2000; 1965
• 24 Typical Procedure for Compound 6 A degased solution of dyine-containing aminophosphonate (0.39 mmol), alkyne (1.55 mmol, 4 equiv), and Grubbs II catalyst (0.02 mmol, 5 mol%) in dry CH₂Cl₂ (8 mL) was stirred under heating at 60 °C for 3 h. After cooling to r.t., the solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica gel (eluent: CH₂Cl₂–EtOAc) to afford the product. Selected Data for Compound 6b ¹H NMR (300 MHz, CDCl₃): δ = 0.98 (t, J = 7.3 Hz, 3 H, CH₃), 1.07 (t, J = 7.1 Hz, 3 H, CH₃), 1.17 (t, J = 6.5 Hz, 3 H, CH₃), 1.32–1.45 (m, 2 H, CH₂), 1.61–1.71 (m, 2 H, CH₂), 2.68 (t, J = 7.6 Hz, 2 H, CH₂), 3.52–3.56 (m, 2 H, CH₂), 3.89–4.20 (m, 4 H, OCH₂), 4.76 (br s, 2 H, CH₂), 5.21 (d, J = 12.2 Hz, 1 H, OCH₂), 5.35 (d, J = 12.2 Hz, 1 H, OCH₂), 7.08–7.21 (m, 2 H, ArH), 7.32–7.52 (m, 10 H, ArH). ¹⁹F NMR (282 MHz, CDCl₃): δ = 9.81 (s, 3 F, CF₃). ³¹P NMR (161 MHz, CDCl₃): δ = 16.63 (q, J = 3.3 Hz). ¹³C NMR (151 MHz, CDCl₃): δ = 13.9, 15.8 (d, J = 6.6 Hz), 16.2 (d, J = 5.5 Hz), 22.4, 33.6, 35.3, 43.4, 47.3, 62.7 (d, J = 8.8 Hz), 64.0 (m), 64.8 (dq, J = 28.7, 154.8 Hz), 67.9, 124.7, 125.9 (qd, J = 12.8, 288.9 Hz), 127.1, 127.2 (d, J = 6.6 Hz), 128.1, 128.2, 128.3, 128.4, 129.2, 129.4, 136.2, 140.2, 140.6, 141.6, 155.7, 171.1. Anal. Calcd for C₃₂H₃₇F₃NO₅P: C, 63.67; H, 6.18; N, 2.32. Found: C, 63.28; H, 5.88; N, 2.54