Gold-catalyzed cyclization of Baylis–Hillman adducts derived from formyl-indoles

¹ Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain;
² Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, IQOG-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain

Published: 01 November 2016 by MDPI in The 20th International Electronic Conference on Synthetic Organic Chemistry session General Organic Synthesis

https://doi.org/10.3390/ecsoc-20-a003

Abstract:

Indoles are important structural motifs found in biological and pharmacological compounds.[1] Therefore, the construction and functionalization of indole skeletons has attracted considerable attention. On the other hand, the use of gold salts has gained a lot of attention in the recent times because of their powerful soft Lewis acidic nature. Such a property allows gold catalysts to activate unsaturated functionalities such as alkynes, alkenes, and allenes, to create C–C bonds under extremely mild conditions.[2] Moreover, Baylis–Hillman (BH) adducts are usually flexible and multifunctional products which can be easily transformed in a huge number of derivatives.[3] However, although many efforts have been made in these fields, the gold-catalyzed reactions using BH adducts derived from formyl-indoles as substrates constitute an unexplored field of noble metal catalysis. In our continuing efforts on the construction of potentially bioactive heterocycles,[4] we wish to report now details of the gold-catalyzed direct synthesis of dihydrocyclopenta[b]indoles from indole-tethered a-hydroxacrylates (Baylis–Hillman adducts) derived from formyl-indoles. The newly formed five-membered ring arises from a selective indole hydroarylation followed by dehydration.

[1] (a) Kaushik,N. K.;Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620. (b) Vicente, R. Org. Biomol. Chem. 2011, 9, 6469.

[2] (a) Hashmi, A. S. K. Acc. Chem. Res. 2014, 47, 864; (b) Obradors, C.; Echavarren, A. M. Acc. Chem. Res. 2014, 47, 902; (c) Alcaide, B.; Almendros, P. Acc.Chem. Res. 2014, 47, 939.

[3] (a) Wei, Y.; Shi, M. Chem. Rev. 2013, 113, 6659; (b) Liu, T.-Y.; Xiec, M.; Chen, Y.-C. Chem. Soc. Rev. 2012, 41, 4101; (c) Singh, V.; Batra. S. Tetrahedron 2008, 64, 4511.

[4] (a) Alcaide, B.; Almendros, P.; Aragoncillo, C.; Fernández, I.; Gómez-Campillos, G. Chem. Eur. J. 2016, 22, 285; (b) Alcaide, B.; Almendros, P.; Fernández, I.; Martín-Montero, R.; Martínez-Peña, F.; Ruiz, M. P.; Torres, M. R. ACS Catal. 2015, 5, 4842. (c) Alcaide, B.; Almendros, P.; Alonso J.-M.; Fernández, I.; Chemm. Commun. 2012, 48, 6604.

Keywords: Baylis–Hillman, indoles, gold catalysis

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