Palladium-Catalyzed Synthesis of Polysubstituted Pyrazoles by Ring-Opening Reactions of 2H-Azirines with Hydrazones

Abstract

A palladium–catalyzed ring-opening reaction of 2H-azirines with hydrazones has been developed. This protocol provides an alternative route for the construction of various polysubstituted pyrazoles with a wide substrate scope. Moreover, a plausible mechanism is proposed for this reaction, which should further enrich the chemical conversion of 2H-azirines.

Key words

palladium catalysis - ring opening - azirines - hydrazones - pyrazoles

Publication History

Received: 21 June 2020

Accepted after revision: 28 July 2020

Article published online:
28 August 2020

• References and Notes


For reviews on 2H-azirine chemistry, see:
• 1a Nakamura S. Chem. Asian J. 2019; 14: 1323
• 1b Huang C.-Y, Doyle AG. Cm. Rev. 2014; 114: 8153
• 1c Khlebnikov AF, Novikov MS. Tetrahedron 2013; 69: 3363
• 1d Palacios F, Ochoa de Retana AM, Martínez de Marigorta E, de los Santos JM. Eur. J. Org. Chem. 2001; 2001: 2401
• 2a Sujatha C, Bhatt CS, Ravva MK, Suresh AK, Namitharan K. Org. Lett. 2018; 20: 3241
• 2b Prechter A, Henrion G, Faudot dit Bel P, Gagosz F. Angew. Chem. Int. Ed. 2014; 53: 4959
• 2c Jiang Y, Park C.-M, Loh T.-P. Org. Lett. 2014; 16: 3432
• 2d Loy NS. Y, Singh A, Xu X, Park C.-M. Angew. Chem. Int. Ed. 2013; 52: 2212
• 3a Loy NS. Y, Kim S, Park C.-M. Org. Lett. 2015; 17: 395
• 3b Ryu T, Baek Y, Lee PH. J. Org. Chem. 2015; 80: 2376 ; corrigendum: J. Org. Chem. 2015, 80, 9804
• 3c Wang Y, Lei X, Tang Y. Chem. Commun. 2015; 51: 4507
• 4a Zhu L, Yu Y, Mao Z, Huang X. Org. Lett. 2015; 17: 30
• 4b Li T, Xin X, Wang C, Wang D, Wu F, Li X, Wan B. Org. Lett. 2014; 16: 4806
• 4c Filho Faria dos Santos P, Schuchardt U. Angew. Chem. Int. Ed. 1977; 16: 647
• 4d Zhao M.-N, Ren Z.-H, Yang D.-S, Guan Z.-H. Org. Lett. 2018; 20: 1287
• 4e Li T, Yan H, Li X, Wang C, Wan B. J. Org. Chem. 2016; 81: 12031
• 4f Galenko EE, Shakirova FM, Bodunov VA, Novikov MS, Khlebnikov AF. Org. Biomol. Chem. 2020; 18: 2283
• 5a Taber DF, Tian WW. J. Am. Chem. Soc. 2006; 128: 1058
• 5b Jana S, Clements MD, Sharp BK, Zheng N. Org. Lett. 2010; 12: 3736
• 5c Thangaraj M, Bhojgude SS, Jain S, Gonnade RG, Biju AT. J. Org. Chem. 2016; 81: 8604
• 5d Khaidarov AR, Rostovskii NV, Zolotarev AA, Khlebnikov AF, Novikov MS. J. Org. Chem. 2019; 84: 3743
• 6a Rossa TA, Fantinel M, Bortoluzzi AJ, Sá MM. Eur. J. Org. Chem. 2018; 2018: 4171
• 6b Angyal A, Demjén A, Wölfling J, Puskás LG, Kanizsai I. J. Org. Chem. 2020; 85: 3587
• 6c Shi S, Xu K, Jiang C, Ding Z. J. Org. Chem. 2018; 83: 14791
• 6d Cardoso AL, Lemos A, Pinhoe e Melo TM. V. D. Eur. J. Org. Chem. 2014; 2014: 5159
• 6e Auricchio S, Grassi S, Malpezzi L, Sartori AS, Truscello AM. Eur. J. Org. Chem. 2001; 1183
• 6f Müller F, Mattay J. Angew. Chem. Int. Ed. 1991; 30: 1336
• 7a Serebryannikova AV, Galenko EE, Novikov MS, Khlebnikov AF. J. Org. Chem. 2019; 84: 15567
• 7b Duan X, Yang K, Lu J, Kong X, Liu N, Ma J. Org. Lett. 2017; 19: 3370
• 7c Ning Y, Otani Y, Ohwada T. J. Org. Chem. 2017; 82: 6313
• 7d Zeng T.-T, Xuan J, Ding W, Wang K, Lu L.-Q, Xiao W.-J. Org. Lett. 2015; 17: 4070
• 7e Shah RS, Navathel SS, Dikundwar AG, Row TN. G, Vasella AT. Eur. J. Org. Chem. 2013; 2013: 264
• 8a Zhou W, Zhang M, Li H, Chen W. Org. Lett. 2017; 19: 10
• 8b Sakharov AP, Rostovskii NV, Khlebnikov AF, Panikorovskii TL, Novikov MS. Org. Lett. 2019; 21: 3615
• 8c Pawar SK, Sahani L, Liu R.-S. Chem. Eur. J. 2015; 21: 10843
• 8d Molina A, Díaz-Tendero S, Adrio J, Carretero JC. Chem. Commun. 2020; 56: 5050
• 8e Smetanin IA, Agafonova AV, Rostovskii NV, Khlebnikov AF, Yufit DS, Novikov MS. Org. Chem. Front. 2020; 7: 525
• 9a Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. J. Med. Chem. 2012; 55: 8630
• 9b Liu J.-J, Sun J, Fang Y.-B, Yang Y.-A, Jiao R.-H, Zhu H.-L. Org. Biomol. Chem. 2014; 12: 998
• 9c Habeeb AG, Praveen Rao PN, Knaus EE. J. Med. Chem. 2001; 44: 3039
• 9d Dai H.-X, Stepan AF, Plummer MS, Zhang Y.-H, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 7222
• 10 Pérez-Fernández R, Goya P, Elguero J. ARKIVOC 2014; 233
• 11 Ansari A, Ali A, Asif M, Shamsuzzaman S. New J. Chem. 2017; 41: 16
• 12 Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot YN, Al-Aizari FA, Ansar M. Molecules 2018; 23: 134
• 13 Fustero S, Sánchez-Roselló M, Barrio P, Simón-Fuentes A. Chem. Rev. 2011; 111: 6984
• 14 Wu F, Zhang M, Zhou W, Chen W, Liu M, Wu H. J. Org. Chem. 2018; 83: 5999
• 15 Zhao J, Goldman AS, Hartwig JF. Science 2005; 307: 1080
• 16 Koroleff F. Determination of Total Nitrogen in Natural Waters by Means of Persulfate Oxidation, International Council for the Exploration of the Sea (ICES), Council Meeting (2nd ed.), Paper C:8 1969. 1970 ; ICES: Copenhagen; (accesed Aug 24, 2020) http://ices.dk/sites/pub/CM%20Doccuments/1969/C/1969_C8.pdf
• 17 Polysubstituted Pyrazoles 3a–t; General ProcedureThe appropriate 2H-azirine (1; 1.05 mmol), hydrazone 2 (1.0 mmol), Pd(OAc)₂ (10 mol%), K₂S₂O₈ (2.0 mmol), CsF (1.0 mmol), and anhyd 1,4-dioxane (6 mL) were sequentially added to a sealed tube under N₂, and the mixture was stirred at 100 °C for about 12 h until the reaction was complete (TLC). The mixture was then filtered through diatomite, and the filter cake was washed with EtOAc(10 mL). The filtrate was collected and concentrated under reduced pressure, and the crude product was purified by chromatography [silica gel, PE–EtOAc (40:1)].3-(4-Bromophenyl)-1,4-diphenyl-1H-pyrazole (3a)Yellow solid; yield: 281 mg (75%); mp 113.4–114.7 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 8.78 (s, 1 H), 7.95 (d, J = 7.8 Hz, 2 H), 7.59 (d, J = 8.5 Hz, 2 H), 7.54 (t, J = 7.9 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.41–7.31 (m, 6 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 148.2, 139.3, 132.2, 132.1, 131.4, 129.9, 129.5, 128.6, 128.3, 128.3, 127.1, 126.5, 122.2, 121.3, 118.4. HRMS (ESI): m/z [M+ H]⁺ calcd for C₂₁H₁₆BrN₂: 375.0491; found: 375.0492.