Departamento de Química Orgánica and Centro de Innovación en Química Avanzada (ORFEOCINQA). Universidad de Alicante, Apdo. 99, E-03080-Alicante, Spain
Azabicycles such as pyrrolizidine  and indolizidine  alkaloids are important natural products and their structural motifs are present in many biologically active compounds. Efficient strategies have been developed for the synthesis of different kind of these types of heterocyclic compounds. 1,3-Dipolar cycloadditions (1,3-DC) involving azomethine ylides and electrophilic alkenes are good examples for the synthesis of prolines and these types of azabicycles. Especially interesting are multicomponent  1,3- DC generating in situ the corresponding azomethine ylide from the carbonyl compound and the amine. In this lecture, the synthesis of highly substituted pyrrolizidines would be described by means of thermal and silver mediated multicomponent 1,3-DC between heterocyclic α-amino esters hydrochlorides, dipolarophiles and.aldehydes. This process takes place in a regio- and diastereoselective manner giving highly substituted pyrrolizidines . The corresponding highly substituted indolizidines can be also synthesized by the multicomponent 1,3-dipolar cycloaddition between pipecolic acid methyl ester hydrochloride, aldehydes and dipolarophiles .
 M. Brambilla, S. G. Davies, A. M. Fletcher and J. E. Thompson, Tetrahedron: Asymmetry 25, 387 (2004).
 A. Khashper and W. D. Lubell, Org. Biomol. Chem. 12, 5052 (2014).
 S. Brauch, S. S. van Berkel and B. Westermann, Chem. Soc. Rev. 42, 4948 (2013).
 (a) J. Mancebo-Aracil, C. Nájera, and J. M. Sansano, Chem. Commun. 49, 11218 (2013); (b) J. Mancebo-Aracil, C. Nájera, L. M. Castelló, J. M. Sansano, O. Larrañaga, A. De Cózar and F. P. Cossío, Tetrahedron 71, 9645 (2015).
 This work has been supported by the Spanish Ministerio de Ciencia e Innovación (MICINN) (Consolider INGENIO 2010 CSD2007-00006, CTQ2010-20387) and Ministerio de Economía y Competitividad (MINECO) (CTQ2013-43446P, CTQ2014- 51912-REDC), FEDER, Generalitat Valenciana (PROMETEO/2009/039 and 2014/017), and by the University of Alicante.