Molybdenum-Mediated One-Pot Synthesis of Pyrazoles from Isoxazoles

Abstract

A one-pot approach for the direct synthesis of substituted pyrazoles from isoxazoles is reported. The process involves isoxazole N–O bond cleavage mediated by a molybdenum complex, in situ hydrolysis of the resulting β-amino enone to the corresponding 1,3-diketone, followed by pyrazole formation in the presence of hydrazine or substituted hydrazine. Good to excellent yields and regioselectivities are obtained with nonsymmetric isoxazoles. By using readily available starting materials, a wide range of substituted pyrazoles may be synthesized by this method.

Key words

isoxazole - pyrazole - molybdenum - one-pot - β-amino enone

• References


For recent reviews on the synthesis of pyrazoles, see:
• 1a Ansari A, Ali A, Asif M. Shamsuzzaman, New J. Chem. 2017; 41: 16
• 1b Fustero S, Sanchez-Rosello M, Barrio P, Simon-Fuentes A. Chem. Rev. 2011; 111: 6984
• 1c Yoon J.-Y, Lee S, Shin H. Curr. Org. Chem. 2011; 15: 657
• 1d Fustero S, Simon-Fuentes A, Sanz-Cervera JF. Org. Prep. Proced. Int. 2009; 41: 253

For recent reviews on pyrazoles in medicinal chemistry, see:
• 2a Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot YN, Al-aizari FA, Ansar M. Molecules 2018; 23: 134
• 2b Keter FK, Darkwa J. Biometals 2012; 25: 9
• 2c Tambe SK, Dighe NS, Pattan SR, Kedar MS, Musmade DS. Pharmacologyonline 2010; 2: 5
• 2d Elguero J, Goya P, Jagerovic N, Silva AM. S. Targets Heterocycl. Syst. 2002; 6: 52
• 3 Knorr L. Ber. Dtsch. Chem. Ges. 1883; 16: 2587
• 4 Hurtley WR. H. J. Chem. Soc. 1929; 1870

For recent reviews on α-arylation of carbonyl compounds, see:
• 5a Bellina F, Rossi R. Chem. Rev. 2010; 110: 1082
• 5b Johansson CC. C, Colacot TJ. Angew. Chem. Int. Ed. 2010; 49: 676
• 5c Evano G, Blanchard N, Toumi M. Chem. Rev. 2008; 108: 3054
• 6 Jiang Y, Wu N, He M. Synlett 2005; 2731
• 7a Xing Q, Lv H, Xia C, Li F. Chem. Eur. J. 2015; 21: 1
• 7b He C, Guo S, Huang L, Lei A. J. Am. Chem. Soc. 2010; 132: 8273
• 8 For a recent review on the synthesis and reactivity of isoxazoles, see: Melo T. Curr. Org. Chem. 2005; 9: 925
• 9 Sviridov S, Vasil’ev AA, Shorshnev SV. Tetrahedron 2007; 63: 12195
• 10a Calle M, Calvo LA, González-Ortega A, González-Nogal AM. Tetrahedron 2006; 62: 611
• 10b Saxena R, Singh V, Batra S. Tetrahedron 2004; 60: 10311
• 10c Akiba K, Kashiwagi K, Ohyama Y, Yamamoto Y, Ohkata K. J. Am. Chem. Soc. 1985; 107: 2721
• 11a Caplan JF, Zheng RJ, Blanchard JS, Vederas JC. Org. Lett. 2000; 2: 3857
• 11b Vergelli C, Giovannoni MP, Pieretti S, Di Giannuario A, Dal Piaz V, Biagini P, Biancalani C, Graziano A, Cesari N. Bioorg. Med. Chem. 2007; 15: 5563
• 12a Keserü GM, Dienes Z, Nógrádi M. J. Org. Chem. 1993; 58: 6725
• 12b Oster TA, Harris TM. J. Org. Chem. 1983; 48: 4307
• 13 Auricchio S, Bini A, Pastomerlo E, Truscello AM. Tetrahedron 1997; 53: 10911
• 14 Angibaud PR, Venet MG, Filliers W, Broeckx R, Ligny YA, Muller P, Poncelet VS, End DW. Eur. J. Org. Chem. 2004; 479
• 15a Fan XS, Zhang YM. Tetrahedron Lett. 2002; 43: 7001
• 15b Natale NR. Tetrahedron Lett. 1982; 23: 5009
• 16a Nitta M, Kobayashi T. J. Chem. Soc., Chem. Commun. 1982; 877
• 16b Nitta M, Kobayashi T. J. Chem. Soc., Perkin Trans. 1 1985; 1: 1401
• 17 Heating at 70 °C is necessary to force the dehydration of the 5-hydroxy-5-trifluoromethylpyrazoline intermediate, see: Fustero S, Román R, Sanz-Cervera J.-F, Simón-Fuentes A, Cuñat AC, Villanova S, Murguía M. J. Org. Chem. 2008; 73: 3523 ; and references herein

For trifluoromethylated pyrazole synthesis, see:
• 18a Martins MA. P, Marzari MR. B, Frizzo CP, Zanatta M, Buriol L, Andrade VP, Bonacorso HG. Eur. J. Org. Chem. 2012; 7112
• 18b Singh PS, Kumar D, Batra H, Naithani R, Rozas I, Elguero J. Can. J. Chem. 2000; 78: 1109
• 19 Zora M, Kivrak A. J. Org. Chem. 2011; 76: 9379
• 20 Xu Z.-L, Li H.-X, Ren Z.-G, Du W.-Y, Xu W.-C, Lang J.-P. Tetrahedron 2011; 67: 5282
• 21 Voronin VV, Ledovskaya MS, Gordeev EG, Rodygin KS, Ananikov VP. J. Org. Chem. 2018; 83: 3819
• 22 Smith H. J. Chem. Soc. 1953; 803