Diversity-Oriented Synthesis via Catalyst-Free Addition of Ketones to [e]-Fused 1H-Pyrrole-2,3-diones

Abstract

A facile synthetic approach towards two distinct pyrrole-based heterocyclic scaffolds has been developed by the interaction of 1H-pyrrole-2,3-diones fused at the [e]-side to a 1,4-benzoxazin-2-one or quinoxalin-2(1H)-one moiety with ketones. The described interaction proceeds either as an aldol reaction or as a Michael addition/intramolecular cyclization depending on the reaction conditions. The disclosed aldol reaction proceeds with good diastereoselectivity under catalyst-free conditions when the reaction is carried out in aromatic hydrocarbons. Products of the cascade Michael addition/intramolecular cyclization reaction are predominantly formed under catalyst-free and solvent-free conditions. The proposed strategy provides facile access to pharmaceutically interesting pyrrole-based polyheterocycles.

Key words

aldol reaction - fused-ring systems - Michael addition - nitrogen heterocycles - polycycles

• References

• 1a Galloway WR. J. D. Isidro-Llobet A. Spring DR. Nat. Commun. 2010; 1: 80
• 1b Garcia-Castro M. Zimmermann S. Sankar MG. Kumar K. Angew. Chem. Int. Ed. 2016; 55: 7586
• 2a Sharma V. Jaiswal PK. Yadav DK. Saran M. Prikhodko J. Mathur M. Swami AK. Mashevskaya IV. Chaudhary S. Acta Chim. Slov. 2017; 64: 988
• 2b Sharma V. Jaiswal PK. Saran M. Yadav DK. Saloni, Mathur M. Swami AK. Misra S. Kim M. Chaudhary S. Front. Chem. 2018; 6: 56 ; DOI: 10.3389/fchem.2018.00056
• 3 Jaiswal PK. Sharma V. Kumar S. Mathur M. Swami AK. Yadav DK. Chaudhary S. Arch. Pharm. Chem. Life Sci. 2018; 1
• 4a Li X. Liu N. Zhang H. Knudson SE. Slayden RA. Tonge PJ. Bioorg. Med. Chem. Lett. 2010; 20: 6306
• 4b Sharma R. Yadav L. Lal J. Jaiswal PK. Mathur M. Swami AK. Chaudhary S. Bioorg. Med. Chem. Lett. 2017; 27: 4393
• 5a Wu P.-L. Hsu Yu-L. Jao Ch.-W. J. Nat. Prod. 2006; 69: 1467
• 5b Mason JJ. Bergman J. Janosik T. J. Nat. Prod. 2008; 71: 1447
• 5c Wang XF. Guan F. Ohkoshi E. Guo W. Wang L. Zhu DQ. Wang SB. Wang LT. Hamel E. Yang D. Li L. Qian K. Morris-Natschke SL. Yuan S. Lee KH. Xie L. J. Med. Chem. 2014; 57: 1390
• 6 Martins Alho MA. Marrero-Ponce Y. Barigye SJ. Meneses-Marcel A. Machado Tugores Y. Montero-Torres A. Gómez-Barrio A. Nogal JJ. García-Sánchez RN. Vega MC. Rolón M. Martínez-Fernández AR. Escario JA. Pérez-Giménez F. Garcia-Domenech R. Rivera N. Mondragón R. Mondragón M. Ibarra-Velarde F. Lopez-Arencibia A. Martín-Navarro C. Lorenzo-Morales J. Cabrera-Serra MG. Piñero J. Tytgat J. Chicharro R. Arán VJ. Bioorg. Med. Chem. 2014; 22: 1568
• 7 Monforte AM. Logoteta P. Ferro S. De Luca L. Iraci N. Maga G. Clercq ED. Pannecouque C. Chimirri A. Bioorg. Med. Chem. 2009; 17: 5962
• 8a Grewal AS. Int. J. Pharm. Res. 2014; 6: 1
• 8b Priyanka P. Pritam S. Cent. Nerv. Syst. Agents Med. Chem. 2015; 15: 28
• 8c Xu Z. Zhang S. Gao C. Fan J. Zhao F. Lv Z.-S. Feng L.-S. Chin. Chem. Lett. 2017; 28: 159
• 8d Medvedev A. Buneeva O. Gnedenko O. Ershov P. Ivanov A. BioFactors 2018; 44: 95
• 9 Chen WB. Liao YH. Du XL. Zhang XM. Yuan WC. Green Chem. 2009; 11: 1465
• 10a Borad MA. Bhoi MN. Prajapati NP. Patel HD. Synth. Commun. 2014; 44: 897
• 10b Borad MA. Bhoi MN. Prajapati NP. Patel HD. Synth. Commun. 2014; 44: 1043
• 10c Saraswat P. Jeyabalan G. Hassan MZ. Rahman MU. Nyola NK. Synth. Commun. 2016; 46: 1643
• 11a Tutynina NM. Racheva NL. Maslivets VA. Aliev ZG. Maslivets AN. Russ. J. Org. Chem. 2013; 49: 95
• 11b Konovalova VV. Shklyaev YuV. Maslivets AN. ARKIVOC 2015; (i): : 48
• 12 Stepanova EE. Maslivets AN. Russ. J. Org. Chem. 2014; 50: 1380
• 13a Bozdyreva KS. Smirnova IV. Maslivets AN. Russ. J. Org. Chem. 2005; 41: 1081
• 13b Mashevskaya IV. Mokrushin IG. Bozdyreva KS. Maslivets AN. Russ. J. Org. Chem. 2011; 47: 253
• 13c Maslivets AN. Mashevskaya IV. Smirnova LI. Krasnykh OP. Shurov SN. Andreichikov YuS. Zh. Org. Khim. 1992; 28: 2545
• 13d Stepanova EE. Babenysheva AV. Maslivets AN. Russ. J. Org. Chem. 2011; 47: 937
• 14 Jaiswal P. Sharma V. Prikhodko J. Mashevskaya IV. Chaudhary S. Tetrahedron Lett. 2017; 58: 2077