Unified Approach to Pyrazole-Fused Heterocyclic and Carbocyclic Motifs through One-Pot Condensation and Intramolecular Dipolar Cycloaddition Reaction

Abstract

A one-pot synthesis of highly substituted pyrazoles that are fused to dihydrochromenes, dihydroquinolines and cyclopentane motifs, from readily available precursors is reported. The reaction involves conversion of alkyne-tethered aldehydes into the corresponding tosylhydrazones, base-mediated generation of diazo compounds, and subsequent intramolecular dipolar cycloaddition reaction. A range of internal and terminal alkynes as well as bromoalkyne compounds can be employed as the tethered dipolarophile to afford the corresponding cycloadducts.

Key words

intramolecular dipolar cycloaddition - pyrazoles - tosyl hydrazones - diazo compounds - alkynes

• References

• 1 New address: T. D. Suja, Department of Chemistry, Central University of Haryana, Mahendergarh, Haryana 123 029, India.
• 2a Elguero J. Pyrazoles . In Comprehensive Heterocyclic Chemistry II . Vol. 3. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 1
• 2b Lamberth C. Heterocycles 2007; 71: 1467
• 2c Singh P, Paul K, Holzer W. Bioorg. Med. Chem. 2006; 14: 5061
• 2d Di Parsia MT, Suarez C, Vitolo MJ, Marquez VE, Beyer B, Urbina C, Hurtado I. J. Med. Chem. 1981; 24: 117
• 3a Heller ST, Natarajan SR. Org. Lett. 2006; 8: 2675
• 3b Kumar SV, Yadav SK, Raghava B, Saraiah B, Ila H, Ragappa KS, Hazra A. J. Org. Chem. 2013; 78: 4960
• 3c Armstrong A, Jones LH, Knight JD, Kelsey RD. Org. Lett. 2005; 7: 713
• 4a Silva VL. M, Silva AM. S, Pinto DC. G. A, Cavaleiro JA. S, Elguero J. Eur. J. Org. Chem. 2004; 4348
• 4b Gosselin F, O’Shea PD, Webster RA, Reamer RA, Tillyer RD, Grabowski EJ. J. Synlett 2006; 3267
• 5a Wu L.-L, Ge Y.-C, He T, Zhang L, Fu X.-L, Fu H.-Y, Chen H, Li R.-X. Synthesis 2012; 44: 1577
• 5b Kong Y, Tang M, Wang Y. Org. Lett. 2014; 16: 576
• 5c Hari Y, Tsuchida S, Sone R, Aoyama T. Synthesis 2007; 3371
• 5d Li P, Zhao J, Wu C, Larock RC, Shi F. Org. Lett. 2011; 13: 3340
• 5e Tufariello JJ In 1,3-Dipolar Cycloaddition Chemistry . Vol. 2. Padwa A. John Wiley & Sons; New York: 1984: 83
• 6a Aggarwal VK, Alonso E, Hynd G, Lydon KM, Palmer MJ, Porcelloni M, Studley JR. Angew. Chem. Int. Ed. 2001; 40: 1430
• 6b Aggarwal VK, de Vicente J, Bonnert RV. Org. Lett. 2001; 3: 2785
• 7 Aggarwal VK, de Vicente J, Bonnert RV. J. Org. Chem. 2003; 68: 5381
• 8 Menon RS, Nair V. Intramolecular 1,3-Dipolar Cycloadditions of Alkenes, Alkynes, and Allenes . In Comprehensive Organic Synthesis . 2nd ed., Vol. 4; Molander GA, Knochel P. Oxford; Elsevier: 2014: 1281-1341
• 9 Nair V, Suja TD. Tetrahedron 2007; 63: 12247
• 10a Wang W.-L, Feng Y.-L, Gao W.-Q, Luo X, Deng W.-P. RSC Adv. 2013; 3: 1687
• 10b Chandrasekhar S, Rajaiah G, Srihari P. Tetrahedron Lett. 2001; 42: 6599
• 10c Yang T, Zhang T, Yang S, Chen S, Li X. Org. Biomol. Chem. 2014; 12: 4290
• 11 Janin YL. Chem. Rev. 2012; 112: 3924
• 12a Sze EM. L, Koh MJ, Tjia YM, Rao W, Chan PW. H. Tetrahedron 2013; 69: 5558
• 12b Jalal S, Bera K, Sarkar S, Paul K, Jana U. Org. Biomol. Chem. 2014; 12: 1759

Compounds 6a and 6b were prepared from 5-hexyn-1-ol through Sonogashira coupling and oxidation, see:
• 13a Moodie LW. K, Larsen DS. Eur. J. Org. Chem. 2014; 1684
• 13b Lu H, Li C, Jiang H, Lizardi CL, Zhang XP. Angew. Chem. Int. Ed. 2014; 53: 7028
• 14 Al-Ayed AS. Molecules 2011; 16: 10292
• 15 Keskin S, Balci M. Org. Lett. 2015; 17: 964
• 16a Probst G, Aubele DL, Bowers S, Dressen D, Garofalo AW, Hom RK, Konradi AW, Marugg JL, Mattson MN, Neitzel ML, Semko CM, Sham HL, Smith J, Sun M, Truong AP, Ye XM, Xu Y.-z, Dappen MS, Jagodzinski JJ, Keim PS, Peterson B, Latimer LH, Quincy D, Wu J, Goldbach E, Ness DK, Quinn KP, Sauer J.-M, Wong K, Zhang H, Zmolek W, Brigham EF, Kholodenko D, Hu K, Kwong GT, Lee M, Liao A, Motter RN, Sacayon P, Santiago P, Willits C, Bard F, Bova MP, Hemphill SS, Nguyen L, Ruslim L, Tanaka K, Tanaka P, Wallace W, Yednock TA, Basi GS. J. Med. Chem. 2013; 56: 5261
• 16b Yin Y, Wu X, Han H.-W, Sha S, Wang S.-F, Qiao F, Lu A.-M, Lv P.-C, Zhu H.-L. Org. Biomol. Chem. 2014; 12: 9157
• 17 Biju AT, Wurz NE, Glorius F. J. Am. Chem. Soc. 2010; 132: 5970