Reactivity studies of thienyl and (oligo)thienylpyrroles

Abstract

Currently, a variety of synthetic approaches to substituted pyrroles exist, although their synthesis, in general, remains challenging. Often, the yields are rather low and a significant number of by-products, such as undesired regioisomers, are obtained. Furthermore, pyrroles are susceptible to chemical degradation as they are rather easily oxidized; this further hampers their synthesis and especially their isolation and purification.1

The chemistry of thienylpyrroles is a very recent field in the chemistry of heterocyclic compounds. In the last few years, synthetic 2-thienylpyrrole derivatives have come in focus. However, even more than 60 years since the first 2-thienylpyrrole: bis-2-[5-(2-thienyl)pyrrole]azametine dihydrochloride) has been reported by Edward Knott2 at Kodak, the synthesis of functionalized thienyl and (oligo)thienylpyrroles remains challenging. Often, the yields are low and the regioselectivity is only modest.3

Before our recent work,3-4 only a few papers were published concerning the regioselectivity studies of 1-(alkyl)aryl-2-thienylpyrrole systems. Following our interest in the chemistry and optical applications of new functionalized systems bearing thiophene and pyrrole rings we have used heterocyclic systems 1 bearing pyrrole and thiophene rings (1, 2 or 3) as precursors for the synthesis of functionalyzed pyrrole derivatives. Compounds 1 have proved to be versatile substrates in several reactions (aromatic electrophilic substitutions: azo coupling, direct tricyanovinylation reaction, Vilsmeier-Haack formylation) and metalation followed by reaction with DMF, allowing the preparation of interesting new donor-acceptor substituted heterocyclic systems, selectively functionalized on the pyrrole 2 or on the thiophene 3 rings. Precursors 1 were prepared through a palladium-catalyzed decarboxylative cross-coupling reaction. The structures of the new compounds were unambiguously confirmed by their analytical and spectral data.

Acknowledgments Thanks are due to the Fundação para a Ciência e Tecnologia (Portugal) and FEDER-COMPETE for financial support through the Centro de Química - Universidade do Minho, Project PTDC/QUI/66251/2006 (FCOMP-01-0124-FEDER-007429), Project PEst-C/QUI/UI0686/2011 (F-COMP-01-0124-FEDER-022716) and a PhD grant to M. C. R. Castro (SFRH/BD/78037/2011). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. References 1. Schmuch, C.; Rupprecht, D. Synthesis 2007, 3095. 2. Knott, E. B. J. Chem. Soc. 1947, 1196. 3. (a) Raposo, M. M. M. in Targets in Heterocyclic Systems: Chemistry and Properties, "Recent developments in the chemistry of 2-thienylpyrroles: synthesis, reactivity and applications", Attanasi, O. A.; Spinelli, D. Eds.; Royal Society of Chemistry: London, 2008, Vol. 11, pp 122-154. 4. (a) Raposo, M. M. M.; Sousa, A. M. R. C.; Fonseca, A. M. C.; Kirsch, G. Tetrahedron 2005, 61, 8249. (b) Raposo, M. M. M.; Sousa, A. M. R. C.; Kirsch, G.; Ferreira, F.; Belsley, M.; Matos Gomes, E.; Fonseca, A. M. C. Tetrahedron 2005, 61, 11991. (c) Raposo, M. M. M.; Sousa, A. M. R. C.; Fonseca, A. M. C.; Kirsch G. Tetrahedron 2006, 62, 3493. (d) Raposo, M. M. M.; Sousa, A. M. R. C.; Kirsch, G.; Cardoso, P.; Belsley, M.; Matos Gomes, E.; Fonseca, A. M. C. Org. Lett. 2006, 8, 3681. (e) Raposo, M. M. M.; Castro, M. C. R.; Schellenberg, P.; Fonseca, A. M. C.; Belsley, M. Tetrahedron 2011, 67, 5189.