Synlett, Table of Contents Synlett 2016; 27(01): 51-56DOI: 10.1055/s-0035-1560526 letter © Georg Thieme Verlag Stuttgart · New York A New Simplified Protocol for Copper(I) Alkyne–Azide Cycloaddition Reactions Using Low Substoichiometric Amounts of Copper(II) Precatalysts in Methanol Benjamin R. Buckley Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK Email: b.r.buckley@lboro.ac.uk Email: m.m.pardo-figueres@lboro.ac.uk Email: amnankhan@gmail.com Email: h.heaney@lboro.ac.uk , Maria M. P. Figueres Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK Email: b.r.buckley@lboro.ac.uk Email: m.m.pardo-figueres@lboro.ac.uk Email: amnankhan@gmail.com Email: h.heaney@lboro.ac.uk , Amna N. Khan Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK Email: b.r.buckley@lboro.ac.uk Email: m.m.pardo-figueres@lboro.ac.uk Email: amnankhan@gmail.com Email: h.heaney@lboro.ac.uk , Harry Heaney* Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK Email: b.r.buckley@lboro.ac.uk Email: m.m.pardo-figueres@lboro.ac.uk Email: amnankhan@gmail.com Email: h.heaney@lboro.ac.uk › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Dedicated to Professor Steven V. Ley FRS for his excellent achievements in organic chemistry on the occasion of his 70th birthday Abstract Copper(II) carboxylates are reduced efficiently by methanol in the presence of alkynes and form yellow alkynylcopper(I) polymeric precatalysts that are involved with azides, in the absence of added ligands, in the catalytic cycles that result in the formation of 1,4-disubstituted 1,2,3-triazoles. Key words Key wordsalkyne - azide - copper(I) - cycloaddition - triazole Full Text References References 1a Tornøe CW, Meldal M. Peptidotriazoles: Copper(I)-Catalysed 1,3-Dipolar Cycloadditions on Solid Phase . In Peptides: Proceedings of the American Peptide Symposium. American Peptide Society and Kluwer Academic Publishers; San Diego: 2001: 263 1b Meldal M, Tornøe CW. J. Org. Chem. 2002; 67: 3057 1c Rostovsev VV, Fokin VV, Green LG, Sharpless KB. Angew Chem. 2002; 114: 2708 For reviews, see for example: 2a Bock VD, Hiemstra H, van Maarseveen JH. Eur. J. Org. Chem. 2006; 51 2b Meldal M, Tornøe CW. Chem. Rev. 2008; 108: 2952 2c Amblard F, Cho JH, Schinazi RF. Chem. Rev. 2009; 109: 4207 2d Themed collection ‘Click chemistry: Function follows form’ in Chem. Soc. Rev. 2010; 39: 1221-1408 2e Topics in Heterocyclic Chemistry. Vol. 28. Košmrlj J. Springer; Berlin/Heidelberg: 2012: 1-232 2f Berg R, Straub BF. Beilstein J. Org. Chem. 2013; 9: 2715 2g Haldón E, Nicasio MC, Pérez PJ. Org. 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S, Alix A, Kumarraja M, Pale P. Chem. Eur. J. 2008; 14: 6713 7 Yousuf SK, Mukherjee D, Singh B, Maity S, Taneja SC. Green Chem. 2010; 12: 1568 8 Wang K, Bi X, Liao P, Fang Z, Meng X, Zhang Q, Liu Q, Ji Y. Green Chem. 2011; 13: 562 9a Lipshutz BH, Taft BR. Angew Chem. 2006; 118: 8415 9b Lee C.-T, Huang S, Lipshutz BH. Adv. Synth. Catal. 2009; 351: 3139 10a Buckley BR, Dann SE, Harris DP, Heaney H, Stubbs EC. Chem. Commun. 2010; 46: 2274 10b Buckley BR, Dann SE, Heaney H. Chem. Eur. J. 2010; 16: 6278 10c Buckley BR, Dann SE, Harris DP, Heaney H, Stubbs EC. Eur. J. Org. Chem. 2011; 770 11 Buckley BR, Butterworth R, Dann SE, Heaney H, Stubbs EC. ACS Catal. 2015; 5: 793 12a Brotherton WS, Michaels HA, Simmons JT, Clark RJ, Dalal NS, Zhu L. Org. Lett. 2009; 11: 4954 12b Kuang G.-C, Michaels HA, Simmons JT, Clark RJ, Zhu L. J. Org. Chem. 2010; 75: 6540 12c Brotherton WS, Guha PM, Phan H, Clark RJ, Shatruk M, Zhu L. 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Chem. 1963; 28: 2163 17c Stephens RD, Castro CE. J. Org. Chem. 1963; 28: 3313 17d Owsley DC, Castro CE. Org. Synth., Coll. Vol. VI 1988; 916 17e Atkinson RE, Curtis RF, Taylor JA. J. Chem. Soc. C 1967; 578 17f Ito H, Arimoto K, Sensui H.-o, Hosomi A. Tetrahedron Lett. 1997; 38: 3977 Glaser reaction products have been observed previously when using Cu(II) salts in the absence of a reducing agent. See: 18a Kamata K, Kotani M, Yamaguchi K, Mizono N. Angew Chem. Int. Ed. 2008; 47: 2407 18b Kamata K, Nakagawa Y, Tamaguchi K, Mizono N. J. Am. Chem. Soc. 2008; 130: 15304 19 Bistriazole Prepared from 1,7-Octadiyne and Benzyl Azide 20 Benzyl azide (0.15 g, 1.1 mmol) and 1,7-octadiyne (0.053 g, 0.5 mmol) were added to a 3 mL vial containing MeOH (2 mL) which was fitted with a magnetic stirrer bar. Copper(II) acetate mono-hydrate was added (1 mg, 0.005 mmol, 0.1 mL from a stock solution in MeOH containing 10 mg/mL), and the vial was closed. The reaction mixture was then stirred and heated at 50 °C for 4 h on a stirrer hotplate fitted with an aluminium vial holder and allowed to cool. The colourless precipitate was filtered, washed with cold MeOH (2 × 5 mL), Et2O (5 mL), and allowed to dry in air to give colourless crystals (0.13 g, 72%); mp 156–158 °C. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.34 (6 H, m), 7.26–7.22 (4 H, m), 7.17 (2H, s), 5.47 (4 H, s), 2.72–2.68 (4 H, m), 1.72–1.69 (4 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.7, 135.2, 129.3, 128.8, 128.2, 120.9, 54.2, 29.1, 25.7 ppm. HRMS: m/z calcd for C22H24N6Na [M + Na]: 395.1960; found: 3955.1959. 20 Saha S, Kaur M, Bera JK. Organometallics 2015; 34: 3047 21 Bistriazole Prepared from 1,8-Nonadiyne and Benzyl Azide 22 A similar reaction gave colourless crystals (0.13 g, 69%); mp 121–123 °C. 1H NMR (400 MHz, CDCl3): δ = 7.37–7.35 (6 H, m), 7.26–7.22 (4 H, m), 7.17 (2 H, s), 5.48 (4 H, s), 2.67 (4 H, t, J = 9.6 Hz), 1.71–1.60 (4 H, m), 1.40–1.37 (2 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.9, 135.2, 129.3, 128.8, 128.2, 120.8, 54.2, 29.3, 28.9, 25.8 ppm. HRMS: m/z calcd for C23H26N6Na [M + Na]: 409.2117; found: 409.2113. 22 Smith CD, Baxendale IR, Lanners S, Hayward JJ, Smith SC, Ley SV. Org. Biomol. Chem. 2007; 5: 1559 23 Triazole Prepared from p-Tolylethyne and 3-Trifluoromethylbenzyl Azide (Table 2, Entry 2) 3-Trifluoromethylbenzyl azide (0.34 g, 1.7 mmol) and p-tolylethyne (0.30 g, 2.6 mmol) were added to a microwave tube (5 mL) fitted with a magnetic stirrer bar. Copper (II) acetate monohydrate (3.4 mg, 0.017 mmol) was added and the mixture suspended in MeOH (5 mL). The reaction mixture was then heated in the microwave apparatus at 100 °C for 20 min and allowed to cool. The reaction mixture was added to EtOAc (50 mL) and H2O (50 mL), separated, and the aqueous layer extracted with EtOAc (2 × 50 mL). The EtOAc layers were evaporated under reduced pressure to give an off-white solid which after recystallisation from Et2O gave the product as colourless crystals (0.53g, 98%); mp 128–130 °C. IR: νmax = 3135, 2982, 1665, 1448, 1386 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.74–7.72 (3 H, m), 7.66–7.61 (2 H, m), 7.55–7.48 (2 H, m), 7.25 (2 H, d, J = 7.6 Hz), 5.65 (2 H, s), 2.39 (3 H, s) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.6, 138.2, 135.8, 131.5 (q, J = 32.2 Hz), 131.3, 129.8, 129.6, 127.4, 125.67 (q), 125.62, 124.7 (q, J = 3.7 Hz), 123.5 (q, J = 271.2 Hz), 122.3, 119.6, 119.2, 53.6, 21.4 ppm. HRMS: m/z calcd for C15H24N3F3Na [M + Na]: 340.1032; found: 340.1040. 24a Zuidema E, Bolm C. Chem. Eur. J. 2010; 16: 4181 24b Albaladejo MJ, Alsonso F, Moglie Y, Yus M. Eur. J. Org. Chem. 2012; 3093 24c Buckley BR, Heaney H, Khan AN. Chem. Eur. J. 2012; 18: 3855 24d Zou E.-H, Johansson AJ, Zuidema E, Bolm C. Chem. Eur. J. 2013; 19: 8144 25 Poh J.-S, Tran DN, Battilocchio C, Hawkins JM, Ley SV. Angew Chem. Int. Ed. 2015; 54: 7920 Supplementary Material Supplementary Material Supporting Information