4-Trimethylsilyl-5-iodo-1,2,3-triazole: A Key Precursor for the Divergent Syntheses of 1,5-Disubstituted 1,2,3-Triazoles

Abstract

Bifunctional 4-trimethylsilyl-5-iodo-1,2,3-triazoles (TMSIT) were reported in this paper, which could be efficiently synthesized directly from readily accessible TMS-alkyne, azide, and copper(I) iodide at room temperature. Using TMSIT as key precursors, a divergent protocol for the preparation of 1,5-disubstituted 1,2,3-triazoles was developed via sequential copper/palladium-catalyzed coupling reactions and desilylation in one pot.

Key words

alkyne - silyl-1,2,3-triazole - cycloaddition - divergent syntheses - cross-coupling

• References and Notes


For selected reviews, see:
• 1a Thirumurugan P, Matosiuk D, Jozwiak K. Chem. Rev. 2013; 113: 4905
• 1b Kolb HC, Sharpless KB. Drug Discovery Today 2003; 8: 1128
• 1c Droumaguet CL, Wang C, Wang Q. Chem. Soc. Rev. 2010; 39: 1233
• 1d Amblard F, Cho JH, Schinazi RF. Chem. Rev. 2009; 109: 4207
• 1e Agalave SG, Maujan SR, Pore VS. Chem. Asian J. 2011; 6: 2696
• 1f Holub JM, Kirshenbaum K. Chem. Soc. Rev. 2010; 39: 1325
• 1g Golas PL, Matyjaszewski K. Chem. Soc. Rev. 2010; 39: 1338
• 2a Alvarez R, Velazquez S, San-Felix A, Aquaro S, De Clercq E, Perno C.-F, Karlsson A, Balzarini J, Camarasa MJ. J. Med. Chem. 1994; 37: 4185
• 2b Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RD, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH. J. Med. Chem. 2000; 43: 953
• 2c Li L, Siebrands CC, Yang Z, Zhang L, Guse AH, Zhang L. Org. Biol. Chem. 2010; 50: 1843
• 2d Wacharasindhu S, Bardhan S, Wan Z.-K, Tabei K, Mansour TS. J. Am. Chem. Soc. 2009; 131: 4174
• 2e Ye CF, Gard GL, Winter RW, Syvret RG, Twamley B, Shreeve JM. Org. Lett. 2007; 9: 3841
• 2f Sharpless KB, Fokin VV. Angew. Chem. Int. Ed. 2004; 43: 3928
• 2g Dai Q, Gao W, Liu D, Kapes LM, Zhang X. J. Org. Chem. 2006; 71: 3928

For selected reviews, see:
• 3a Meldal M, Tornoe CW. Chem. Rev. 2008; 108: 2952
• 3b Hein JE, Fokin VV. Chem. Soc. Rev. 2010; 39: 1302
• 3c Kappe CO, Van der Eycken E. Chem. Soc. Rev. 2010; 39: 1280
• 4a Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
• 4b Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
• 4c Doak BC, Scanlon MJ, Simpson JS. Org. Lett. 2011; 13: 537
• 4d Hong V, Presolski SI, Ma C, Finn MG. Angew. Chem. Int. Ed. 2009; 48: 9879
• 4e del Amo DS, Wang W, Jiang H, Besanceney C, Yan AC, Levy M, Liu Y, Marlow LF, Wu P. J. Am. Chem. Soc. 2010; 132: 16893
• 4f Bevilacqua V, King M, Chaumontet M, Nothisen M, Gabillet S, Buisson D, Puente C, Wagner A, Taran F. Angew. Chem. Int. Ed. 2014; 53: 5872
• 4g González-Díez S, Correa A, Cavallo L, Nolan SP. Chem. Eur. J. 2006; 12: 7558
• 4h Winn J, Pinczewska A, Goldup SM. J. Am. Chem. Soc. 2013; 135: 13318
• 4i Deraedt C, Pinaud N, Astruc D. J. Am. Chem. Soc. 2014; 136: 12092
• 4j Bock VD, Hiemstra H, van Maarseveen JH. Eur. J. Org. Chem. 2006; 51
• 5a Katritzky AR, Bobrov S, Kirichenko K, Ji Y, Steel PJ. J. Org. Chem. 2003; 68: 5713
• 5b Danence LJ. T, Gao Y, Li M, Huang Y, Wang J. Chem. Eur. J. 2011; 17: 3584
• 5c Baxendale IR, Ley SV, Mansfield AC, Smith CD. Angew. Chem. Int. Ed. 2009; 48: 4017
• 5d Aucagne V, Hänni KD, Leigh DA, Lusby PJ, Walker DB. J. Am. Chem. Soc. 2006; 128: 2186
• 5e Worrell BT, Ellery SP, Fokin VV. Angew. Chem. Int. Ed. 2013; 52: 13037
• 5f Haldón E, Álvarez E, Nicasio MC, Pérez PJ. Chem. Commun. 2014; 8978
• 5g Winn J, Pinczewska A, Goldup SM. J. Am. Chem. Soc. 2013; 135: 13318
• 5h Lallana E, Fernandez-Megia E, Riguera R. J. Am. Chem. Soc. 2009; 131: 5748
• 6 Boren BC, Narayan S, Rasmussen LK, Zhang L, Zhao H, Lin Z, Jia G, Fokin VV. J. Am. Chem. Soc. 2008; 130: 8923
• 7 Krasiński A, Fokin VV, Sharpless KB. Org. Lett. 2004; 6: 1237
• 8 Kwok SW, Fotsing JR, Fraser RJ, Rodionov VO, Fokin VV. Org. Lett. 2010; 12: 4217
• 9 Wang Y, Xie Y, Qu H, Wang H, Pan Y, Huang F.-P. J. Org. Chem. 2014; 79: 4463
• 10 Cheng G, Zeng X, Shen J, Wang X, Cui X. Angew. Chem. Int. Ed. 2013; 52: 13265
• 11 Koguchi S, Izawa K. ACS Comb. Sci. 2014; 16: 381
• 12a Buckle DR, Outred DJ, Rockell CM, Smith H, Spicer BA. J. Med. Chem. 1983; 26: 251
• 12b Morzherin Y, Prokhorova PE, Musikhin DA, Glukhareva TV, Fan Z. Pure Appl. Chem. 2011; 83: 715
• 12c Anderson MO, Zhang J, Liu Y, Yao C, Phuan P.-W, Verkman AS. J. Med. Chem. 2012; 55: 5942
• 13a Huang J, Macdonald SJ. F, Harrity JP. A. Chem. Commun. 2009; 436
• 13b Coats SJ, Link JS, Gauthier D, Hlasta D. Org. Lett. 2005; 7: 1469
• 13c Veillard R, Bernoud E, Abdellah I, Lohier J.-F, Alayrac C, Gaumont A.-C. Org. Biomol. Chem. 2014; 12: 3635
• 13d Kloss F, Kön U, Jahn BO, Hlasta DJ, Ackerman JH. J. Org. Chem. 1994; 59: 6184
• 14 Hager MD, Göls H, Schubert US. Chem. Asian J. 2011; 6: 2816
• 15a Li L, Zhang G, Zhu A, Zhang L. J. Org. Chem. 2008; 130: 3630
• 15b Li L, Li Y, Li R, Zhu A, Zhang G. Aust. J. Chem. 2011; 64: 1383
• 15c Li L, Li R, Zhu A, Zhang G, Zhang L. Synlett 2011; 874
• 15d Li L, Hao G, Zhu A, Liu S, Zhang G. Tetrahedron Lett. 2013; 54: 6057
• 15e Li L, Hao G, Zhu A, Fan X, Zhang G, Zhang L. Chem. Eur. J. 2013; 19: 14403
• 16a Wu Y.-M, Deng J, Li Y, Chen Q.-Y. Synthesis 2005; 1314
• 16b Brotherton WS, Clark RJ, Zhu L. J. Org. Chem. 2012; 77: 6443
• 16c Wang B, Zhang J, Wang X, Liu N, Chen W, Hu Y. J. Org. Chem. 2013; 78: 10519
• 17 Typical Procedure for the Synthesis of Compounds 2a–dA mixture of 1 (0.15 mmol), TMS-acetylene (0.17 mmol), CuI (0.17 mmol), NBS (0.17 mmol), and DIPEA (0.17 mmol) in MeCN (3 mL) was stirred at r.t. for 12 h. The mixture was evaporated, and the residue was partitioned between EtOAc and H₂O. The organic layer was washed with brine, dried over anhydrous Na₂SO₄, and evaporated. The residue was purified by silica gel column chromatography (MeOH–CH₂Cl₂) to give compound 2.
• 18 Typical Procedure for the Synthesis of Compounds 3a–k A mixture of 2 (0.056 mmol), phenol (0.067 mmol), CuBr (0.0056 mmol), ethyl 2-oxocyclohexanecarboxylate (0.0112 mmol), and Cs₂CO₃ (0.112 mmol) was stirred in MeCN (2.5 mL) at 70 °C for 24 h under a nitrogen atmosphere. The mixture was evaporated, and the residue was partitioned between EtOAc and H₂O. The organic layer was washed with brine, dried over anhydrous Na₂SO₄, and evaporated. The residue was purified by silica gel column chromatography (MeOH–CH₂Cl₂) to give compound 3.
• 19 Lv X, Bao W. J. Org. Chem. 2007; 72: 3863
• 20 Oura I, Shimizu K, Ogata K, Fukuzawa S.-i. Org. Lett. 2010; 12: 1752
• 21 Typical Procedure for the Synthesis of Compounds 4a–d A mixture of 2 (0.056 mmol), thiophenol (0.067 mmol), CuBr (0.0056 mmol), ethyl 2-oxocyclohexanecarboxylate (0.0112 mmol), and Cs₂CO₃ (0.112 mmol) was stirred in MeCN (2.5 mL) at 70 °C for 24 h under a nitrogen atmosphere. After that, TBAF (0.0112 mmol) was added, and the resulted reaction mixture was stirred for 4 h. The solvents were evaporated, and the residue was partitioned between EtOAc and H₂O. The organic layer was washed with brine, dried over anhydrous Na₂SO₄, and evaporated. The residue was purified by silica gel column chromatography (MeOH–CH₂Cl₂) to give compound 4.
• 22 Typical Procedure for the Synthesis of Compounds 5a–c A mixture of 2 (0.056 mmol), iodobenzene (0.067 mmol), Pd(PPh₃)₂Cl₂ (0.0028 mmol), and KOH (0.0112 mmol) was stirred in THF (2.5 mL) at 50 °C for 24 h under a nitrogen atmosphere. After that, TBAF (0.0112 mmol) was added, and the resulted reaction mixture was stirred for 4 h. The solvents were evaporated, and the residue was partitioned between EtOAc and H₂O. The organic layer was washed with brine, dried over anhydrous Na₂SO₄, and evaporated. The residue was purified by silica gel column chromatography (MeOH–CH₂Cl₂) to give compound 5.
• 23 Typical Procedure for the Synthesis of Compounds 6a–c A mixture of 2 (0.056 mmol), iodobenzene (0.067 mmol), Pd(PPh₃)₂Cl₂ (0.0028 mmol), and KOH (0.0112 mmol) was stirred in THF (2.5 mL) at 50 °C for 24 h under a nitrogen atmosphere. After that, TBAF (0.067 mmol) was added, and the resulted reaction mixture was stirred for 4 h. The solvents were evaporated, and the residue was partitioned between EtOAc and H₂O. The organic layer was washed with brine, dried over anhydrous Na₂SO₄, and evaporated. The residue was purified by silica gel column chromatography (MeOH–CH₂Cl₂) to give compound 6.
• 24a Yao T, Campo MA, Larock RC. J. Org. Chem. 2005; 70: 3511
• 24b Chernyaka N, Gevorgyan V. Adv. Synth. Catal. 2009; 351: 1101