Synthesis of Heteroaryl-Substituted Pyrroles via the 1,3-Dipolar Cycloaddition of Unsymmetrical Münchnones and Nitrovinylheterocycles

Abstract

A series of furanyl-, thiophenyl-, and pyrrolo-substituted pyrroles were prepared via the 1,3-dipolar cycloaddition of unsymmetrical münchnones and nitrovinylheterocycles. The regiochemical outcome of the furan and thiophene cycloadditions compares favorably to previously reported cycloadditions with β-nitrostyrene, while the nitrovinylpyrrole cycloadditions mirror the results observed with nitrovinylindole.

Key words

cycloaddition - heterocycles - pyrroles - regioselectivity - münchnone

• References

• 1 Bergman J, Janosik T. Comprehensive Heterocyclic Chemistry III . Vol. 3. Katritzky AR, Ramsden C, Scriven EF. V, Taylor RJ. K. Elsevier; Oxford: 2008: 269-351
• 2a Young IS, Thornton PD, Thompson A. Nat. Prod. Rep. 2010; 27: 1801
• 2b Welsch ME, Snyder SA, Stockwell BR. Curr. Opin. Chem. Biol. 2010; 14: 347
• 2c Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
• 3a Bhardwaj V, Gumber D, Abbot V, Dhiman S, Sharma P. RSC Adv. 2015; 5: 15233
• 3b Li JJ. Pyrroles . In Heterocyclic Chemistry in Drug Discovery . Li JJ. Wiley; Hoboken: 2013. Chap. 2, 18
• 4a Sathyamoorthi G, Soong ML, Ross TW, Boyer JH. Heteroat. Chem. 1993; 4: 603
• 4b Grimsdale AC, Chan KL, Martin RE, Jokisz PG, Holmes AB. Chem. Rev. 2009; 109: 897
• 4c Panzella L, Pezzella A, Arzillo M, Manini P, Napolitano A, d’Ischia M. Tetrahedron 2009; 65: 2032
• 5a Yurovskaya MA, Alekseyev RS. Chem. Heterocycl. Compd. 2014; 49: 1400
• 5b Ferreira VF, de Souza MC. B. V, Cunha AC, Pereira LO. R, Ferreira ML. G. Org. Prep. Proced. Int. 2001; 33: 411
• 6a Gribble GW. Mesoionic Oxazoles. In The Chemistry of Heterocyclic Compounds, Oxazoles: Synthesis, Reactions, and Spectroscopy. Vol. 60. Taylor EC, Wipf P. Wiley; Hoboken: 2003: Part A: 473-576
• 6b Gribble GW. Mesoionic Ring Systems. In The Chemistry of Heterocyclic Compounds: Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Vol. 59. Padwa A, Pearson WH. Wiley; Hoboken: 2002: 681-754
• 7 Lopchuk JM, Hughes RP, Gribble GW. Org. Lett. 2013; 15: 5218
• 8 Lopchuk JM, Gribble GW. Heterocycles 2011; 82: 1617
• 9 Lopchuk JM, Gribble GW. Tetrahedron Lett. 2011; 52: 4106
• 10 Gribble GW, Pelkey ET, Simon WM, Trujillo HA. Tetrahedron 2000; 56: 10133
• 11 Lopchuk JM, Gribble GW. Tetrahedron Lett. 2014; 55: 2809
• 12 Lopchuk JM, Gribble GW. Tetrahedron Lett. 2015; 56 doi: 10.1016/j.tetlet.2014.12.104
• 13 The precursors have been stored on the bench under air for >5 years without any noticeable degradation.
• 14 Bourguignon J, Le Nard G, Queguiner G. Can. J. Chem. 1985; 63: 2354
• 15 Khorana N, Smith C, Herrick-Davis K, Purohit A, Teitler M, Grella B, Dukat M, Glennon RA. J. Med. Chem. 2003; 46: 3930
• 16 Noland WE, Pardi G. J. Heterocycl. Chem. 2005; 42: 1149
• 17 For other examples of münchnones 2 and 14 leading to the same regiochemical outcome, see refs. 7, 8, and 10.