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Article Dans Une Revue Journal of Molecular Catalysis B: Enzymatic Année : 2015

Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions

Résumé

Chemoselective synthesis of N-protected beta-amino esters involving lipase-catalyzed aza-Michael additions and alpha,beta-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity.
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Dates et versions

hal-01268997 , version 1 (05-02-2016)

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Jose Domingo Rivera-Ramirez, Jaime Escalante, Agustin Lopez-Munguia, Alain Marty, Edmundo Castillo. Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions. Journal of Molecular Catalysis B: Enzymatic, 2015, 112, pp.76-82. ⟨10.1016/j.molcatb.2014.12.009⟩. ⟨hal-01268997⟩
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