Carmen Nájera
University of Alicante, Spain
Title: Multicomponent 1,3-Dipolar cycloadditions of azomethine ylides
Biography
Biography: Carmen Nájera
Abstract
Multicomponent reactions (MCRs) are important processes from atom and step economy point of view. 1,3-Dipolar cycloadditions (1,3-DC) involving azomethine ylides and electrophilic alkenes are good examples for this type of transformation but are not so frequently described. In this lecture, the thermal and silver mediated multicomponent 1,3-DC between a-amino esters, dipolarophiles and aldehydes will be considered. This 1,3-DC allows the synthesis of highly substituted pyrrolidines under conventional or MW heating. In general, 4,5-endo diastereoselectivity was mainly observed and 2,5-cis-cycloadducts are formed according to a W-shaped dipole. When this MCR was performed with 2-oxoaldehydes, the 1,3-DC takes place under silver acetate catalysis at rt [3b]. On the other hand, the multicomponent 1,3-dipolar cycloaddition between different proline esters, aldehydes and dipolarophiles afford highly substituted pyrrolizidines will also be described. The corresponding highly substituted pyrrolizidines are obtained in all cases with 2,5-trans-relative configuration between two electron-withdrawing groups and major endo-selectivity with 2,4-cis-relative configuration. The use of (2S,4R)-4-hydroxyproline methyl ester hydrochloride allowed the synthesis of enantiomerically enriched pyrrolizidines. When pipecolic acid alkyl esters are used the corresponding indolizidines can be prepared under thermal reaction conditions.
Recent Publications
[1] (a) Brauch S, van Berkel S S, Westermann B (2013) Higher-order multicomponent reactions: beyond four reactants. Chem. Soc. Rev. 42, 4948-62.
(b) Science of Synthesis: Multicomponent Reactions; Müller, T. J. J. Ed.; Thieme: Stuttgart, 2014. (c) Multicomponent Reactions: Concepts and Applications for Design and Synthesis, Pérez-Herrera, R. and Marqués-López, E. Eds.; Wiley-VCH: Weinheim, 2015.
[2] Nájera, C.; Sansano, J. M.; Yus, M. J. Braz. Chem. Soc. 2010, 21, 377.
[3] (a) Mancebo-Aracil, J.; Nájera, C.; Sansano, J. M. Org. Biomol. Chem. 2013, 11, 662. (b) Mancebo-Aracil, J.; Cayuelas, A.; Nájera, C.; Sansano, J. Tetrahedron 2015, 71, 8804.
[4] (a) Mancebo-Aracil, J.; Nájera, C.; Sansano, J. Chem. Commun. 2013, 49, 11218. (b) Selva, V.; Larrañaga, O.; Castelló, L. M.; Nájera, C.; Sansano, J. M.; de Cózar, A. J. Org. Chem. 2017, 82, 6298.
[5] Castelló, L. M.; Selva, V.; Nájera, C.; Sansano, J. M. Synthesis 2017, 49, 299.