Copper-Catalyzed Synthesis of Alkyl-Substituted Pyrrolo[1,2-a]quinoxalines from 2-(1H-Pyrrol-1-yl)anilines and Alkylboronic Acids

Abstract

A radical pathway for the construction of pyrrolo[1,2-a]quinoxalines by using 2-(1H-pyrrol-1-yl)anilines and alkylboronic acids has been developed. Features of this process include Cu catalysis, readily accessible starting materials, and simple operations. Alkylboronic acids are used for the construction of pyrrolo[1,2-a]quinoxaline derivatives, and the desired products are obtained in moderate yields.

Key words

pyrrolylanilines - alkylboronic acids - pyrroloquinoxalines - radical reaction

• References and Notes

• 1a Torres E, Moreno E, Ancizu S, Barea C, Galiano S, Aldana I, Monge A, Pérez-Silanes S. Bioorg. Med. Chem. Lett. 2011; 21: 3699
• 1b Le T, Yu H, Niu X. Food Chem. 2015; 175: 85
• 1c Su W, Xiao M, Fan Q, Zhong J, Chen J, Dang D, Shi J, Xiong W, Duan X, Tan H, Liu Y, Zhu W. Org. Electron. 2015; 17: 129
• 1d Wang L, Yang X, Wang X, Sun L. Dyes Pigm. 2015; 113: 581
• 1e Carta A, Loriga M, Paglietti G, Mattana AP, Fiori L, Mollicotti P, Sechi L, Zanetti S. Eur. J. Med. Chem. 2004; 39: 195
• 2 Moarbess G, Deleuze-Masquefa C, Bonnard V, Gayraud-Paniagua S, Vidal J.-R, Bressolle F, Pinguetand F, Bonnet P.-A. Bioorg. Med. Chem. 2008; 16: 6601
• 3a Prunier H, Rault S, Lancelot J.-C, Robba M, Renard P, Delagrange P, Pfeiffer B, Caignard D.-H, Misslin R, Hamon M. J. Med. Chem. 1997; 40: 1808
• 3b Butini S, Budriesi R, Hamon M, Morelli E, Gemma S, Brindisi M, Borrelli G, Novellino E, Fiorini I, Ioan P, Chiarini A, Cagnotto A, Mennini T, Fracasso C, Caccia S, Campiani G. J. Med. Chem. 2009; 52: 6946
• 4 Guillon J, Mouray E, Moreau S, Mullié C, Forfar I, Desplat V, Belisle-Fabre S, Pinaud N, Ravanello F, Le-Naour A, Léger J.-M, Gosmann G, Jarry C, Déléris G, Sonnet P, Grellier P. Eur. J. Med. Chem. 2011; 46: 2310
• 5 Cheeseman GW. H, Tuck B. J. Chem. Soc. C. 1966; 852
• 6a Zhang Z, Xie C, Tan X, Song G, Wen L, Gao H, Ma C. Org. Chem. Front. 2015; 2: 942
• 6b Xie C, Feng L, Li L, Ma X, Liu Y, Ma C. Org. Biomol. Chem. 2016; 14: 8529
• 7 Li J, Zhang J, Yang H, Gao Z, Jiang G. J. Org. Chem. 2017; 82: 765
• 8 He Z, Bae M, Wu J, Jamison TF. Angew. Chem. Int. Ed. 2014; 53: 14451
• 9 de Fatima Pereira M, Thiéry V. Org. Lett. 2012; 14: 4754
• 10a An Z, Zhao L, Wu M, Ni J, Qi Z, Yu G, Yan R. Chem. Commun. 2017; 53: 11572
• 10b An Z, Jiang Y, Guan X, Yan R. Chem. Commun. 2018; 54: 10738
• 11a Molander GA, Ellis N. Acc. Chem. Res. 2007; 40: 275
• 11b Darses S, Genet J.-P. Chem. Rev. 2008; 108: 288
• 11c Molander GA, Colombel V, Braz VA. Org. Lett. 2011; 13: 1852
• 11d Tellis JC, Kelly CB, Primer DN, Jouffroy M, Molander GA. Acc. Chem. Res. 2016; 49: 1429
• 11e Sorin G, Martinez Mallorquin R, Contie Y, Baralle A, Malacria M, Goddard J.-P, Fensterbank L. Angew. Chem. Int. Ed. 2010; 49: 8721
• 11f Zhang L, Liu Z.-Q. Org. Lett. 2017; 19: 6594
• 12a Demir AS, Reis Ö, Emrullahoglu M. J. Org. Chem. 2003; 68: 578
• 12b Uchiyama N, Shirakawa E, Nishikawa R, Hayashi T. Chem. Commun. 2011; 47: 11671
• 12c Lv W.-X, Zeng Y.-F, Zhang S.-S, Li Q, Wang H. Org. Lett. 2015; 17: 2972
• 12d Seiple IB, Su S, Rodriguez RA, Gianatassio R, Fujiwara Y, Sobel AL, Baran PS. J. Am. Chem. Soc. 2010; 132: 13194
• 12e Fujiwara Y, Domingo V, Seiple IB, Gianatassio R, Del Bel M, Baran PS. J. Am. Chem. Soc. 2011; 133: 3292
• 12f Tobisu M, Koh K, Furukawa T, Chatani N. Angew. Chem. Int. Ed. 2012; 51: 11363
• 12g Liu D, Liu C, Li H, Lei A. Angew. Chem. Int. Ed. 2013; 52: 4453
• 12h Bering L, Antonchick AP. Org. Lett. 2015; 17: 3134
• 12i Castro S, Fernández J, Fañanás FJ, Vicente R, Rodríguez F. Chem. Eur. J. 2016; 22: 9068
• 12j Li G.-X, Morales-Rivera CA, Wang Y, Gao F, He G, Liu P, Chen G. Chem. Sci. 2016; 7: 6407
• 13 Zhao B, Shi Z. Angew. Chem. Int. Ed. 2017; 56: 12727
• 14 Li L, Chen H, Mei M, Zhou L. Chem. Commun. 2017; 53: 11544
• 15a Zhao J.-F, Gao P, Duan X.-H, Guo L.-N. Adv. Synth. Catal. 2018; 360: 1775
• 15b Wu J, Zhang J.-Y, Gao P, Xu S.-L, Guo L.-N. J. Org. Chem. 2018; 83: 1046
• 15c Zhang J.-Y, Duan X.-H, Yang J.-C, Guo L.-N. J. Org. Chem. 2018; 83: 4239
• 16 4-Propylpyrrolo[1,2-a]quinoxaline (3aa):² Typical Procedure A mixture of 2-(1H-pyrrol-1-yl)aniline (1a; 1 equiv, 0.3 mmol), BuB(OH)₂ (2a; 3 equiv, 0.9 mmol), PivOH (1 equiv, 0.3 mmol), Cu(OPiv)₂ (10 mol%, 0.03 mmol), and DCM (1 mL) was stirred at 80 °C under O₂ (balloon) for 8 h. Upon completion of the reaction (TLC), the mixture was concentrated in vacuo, and the crude product was purified by column chromatography [silica, gel, PE–EtOAc (10:1)] to give a light-yellow solid; yield: (40.3 mg, 73%); mp 45–46 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.94–7.90 (m, 1 H), 7.90–7.89 (m, 1 H), 7.84–7.80 (m, 1 H), 7.49–7.44 (m, 1 H), 7.44–7.39 (m, 1 H), 6.92–6.89 (m, 1 H), 6.85–6.83 (m, 1 H), 3.02–2.97 (m, 2 H), 1.99–1.89 (m, 2 H), 1.10–1.05 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.4, 136.0, 129.4, 127.3, 126.8, 126.1, 125.0, 114.1, 113.6, 113.4, 106.3, 37.8, 22.0, 14.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₅N₂: 211.1230; found: 211.1227.