2-Ethynylpyridine-Promoted Rapid Copper(I) Chloride Catalyzed Azide–Alkyne Cycloaddition Reaction in Water

Abstract

The copper(I) chloride catalyzed reaction of azides with alkynes in water at room temperature was promoted by the addition of a catalytic amount of 2-ethynylpyridine, affording the corresponding 1,4-disubstituted 1,2,3-triazoles in good yields after a specific reaction time. The catalytic system could be successfully applied to electron-rich, electron-poor, and sterically crowded substrates. A study of the additive effect of pyridine derivatives revealed that alkynyl and 2-pyridyl groups were essential for activating the copper catalyst.

Key words

cycloaddition - azides - alkynes - copper - heterocycles

• References and Notes


For reviews on the CuAAC reaction, see:
• 1a Korb HC, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2001; 40: 2004
• 1b Bock VD, Hiemstra H, Maarseveen JH. Eur. J. Org. Chem. 2006; 1: 51
• 1c Meldal M, Tornøe CW. Chem. Rev. 2008; 108: 2952
• 1d Hein JE, Fokin VV. Chem. Soc. Rev. 2010; 39: 1302
• 1e Kappe CO, Eycken EV. Chem. Soc. Rev. 2010; 39: 1280
• 1f Liang L, Astruc D. Coord. Chem. Rev. 2011; 255: 2933
• 1g Struthers H, Mindt TL, Schibli R. Dalton Trans. 2010; 39: 675

For recent selected works on CuAAC reaction, see:
• 1h Özçubukçu S, Ozkai E, Jimeno C, Pericàs MA. Org. Lett. 2009; 11: 4680
• 1i Ozkal E, Özçubukçu S, Jimeno C, Pericàs MA. Catal. Sci. Technol. 2012; 2: 195
• 1j Nakamura T, Terashima T, Ogata K, Fukuzawa S.-i. Org. Lett. 2011; 13: 620
• 1k Yamada YM. A, Sarkar SM, Uozumi Y. J. Am. Chem. Soc. 2012; 134: 9285
• 1l Shin J.-A, Lim Y.-G, Lee K.-H. J. Org. Chem. 2012; 77: 4117
• 1m Berg R, Straub J, Schreiner E, Mader S, Rominger F, Straub B.-F. Adv. Synth. Catal. 2012; 354: 3445
• 2a Click Chemistry for Biotechnology and Materials Science. Lahnn J. John Wiley and Sons; Chichester: 2009

For reviews, see:
• 2b Gil MV, Arévalo MJ. López Ó. Synthesis 2007; 1589
• 2c Binder WH, Sachsenhofer R. Macromol. Rapid. Commun. 2008; 29: 952
• 2d Aragão-Leoneti V, Campo VL, Gomes AS, Field RA, Carvalho I. Tetrahedron 2010; 66: 9475
• 2e Muller T, Bräse S. Angew. Chem. Int. Ed. 2011; 50: 11844

For examples of pyta–metal complexes, see:
• 3a Obata M, Kitamura A, Mori A, Kameyama C, Czaplewska JA, Tanaka R, Kinoshita I, Kusumoto T, Hashimoto H, Harada M, Mikata Y, Funabiki T, Yano S. Dalton Trans. 2008; 3292
• 3b Fletcher JT, Bumgarner BJ, Engels ND, Skoglung DA. Organometallics 2008; 27: 5430
• 3c Schweinfurth D, Pattacini R, Strobel S, Sarkar B. Dalton Trans. 2009; 9291
• 3d Felici M, Contrera-Carballda P, Vida Y, Smits JM. M, Nolte RJ. M, Cola LD, Williams RM, Feiters MC. Chem. Eur. J. 2009; 15: 13124
• 3e Uranker D, Pinter B, Pevec A, De Proft F, Turel I, Košmrlj J. Inorg. Chem. 2010; 49: 4820
• 3f Fleischel O, Wu N, Petitjean A. Chem. Commun. 2010; 46: 8454
• 3g Happ B, Escudero D, Hager MD, Friebe C, Winter A, Görls H, Altuntas E, Gonzáles L, Schubert US. J. Org. Chem. 2010; 75: 4025
• 3h Crowley JD, Bandeen PH, Honton LR. Polyhedron 2010; 29: 70
• 3i Kilpin KJ, Crowley JD. Polyhedron 2010; 29: 3111
• 3j Schweinfurth D, Strobel S, Sarkar B. Inorg. Chim. Acta 2011; 374: 253
• 3k Stengel I, Mishra A, Pootrakulchote N, Moon S.-J, Zakeerruddin SM, Grätzel M, Bäuerle P. J. Mater. Chem. 2011; 21: 3726
• 3l Zhang G, Wang Y, Wen X, Ding C, Li Y. Chem. Commun. 2012; 48: 2979
• 3m Schweinfurth D, Su C.-Y, Wei S.-C, Braunstein P, Sarkar B. Dalton Trans. 2012; 41: 12984
• 4 We obtained the X-ray crystal structure of pyta–CuI complex (see Supporting Information).
• 5 Hohloch et al. demonstrated that the CuI complex with 5 catalyzed the reaction of phenylacetylene with benzylazide under neat conditions, but gave less than 20% yield after 100 min reaction. See: Hohloch S, C.-Y Su, Sarkar B. Eur. J. Inorg. Chem. 2011; 3067
• 6 An equimolar mixture of CuCl and 1 in MeOH (or H₂O) at r.t. overnight afforded a precipitate, which had a strong absorption at 1947 cm^–1 in the IR spectrum attributed to the presence of a Cu acetylide complex. It has been reported that polymeric Cu acetylide complexes catalyze the CuAAC reaction ‘on water’ under microwave irradiation. See: Buckley BR, Dann SE, Heaney H, Stubbs EC. Eur. J. Org. Chem. 2011; 770
• 7 Yoshida and Hosoya reported that the more sterically hindered azide occasionally reacts with a specified alkyne preferentially. See: Yoshida S, Shiraishi A, Kanno K, Matsushita T, Johmoto K, Uekusa H, Hosoya T. Sci. Rep. 2011; 1: 82

Compound 19 has previously been prepared by NHC–Cu complexes:
• 8a Nakamura T, Terashima T, Ogara K, Fukuzawa S.-i. Org. Lett. 2011; 13: 620
• 8b Huang J, Hong J.-T, Hong SH. Eur. J. Org. Chem. 2012; 6630
• 9 General Procedure for 2-Ethynylpyridine-Promoted Cu(I)-Catalyzed Azide–Alkyne 1,3-Dipolar Cycloaddition In a vial containing a magnetic stirrer bar was added CuCl (2.98 mg, 0.03 mmol), H₂O (3 mL), 2-ethynylpyridine (3.0 μL, 0.03 mmol) followed by an alkyne (1.0 mmol) and an azide (1.05 mmol) were loaded. The vial was closed with a screw cap, and the reaction mixture was stirred at specified temperature for the time specified in Table 3. The resulting solution was quenched with NH₃ solution, extracted with EtOAc, washed with brine, dried over MgSO₄, filtered, and finally the solvent was removed under reduced pressure. GC–MS analysis revealed the presence of the corresponding 1,2,3-triazole. The crude product was purified by PTLC or short silica gel column (hexane–EtOAc as eluent)