Bifunctional tripeptide with a phosphonic acid as a bronsted acid for Michael addition: mechanistic insights

Enamine catalysis is a widespread activation mode in the field of organocatalysis and is often encountered in bifunctional organocatalysts. We previously described H-Pro-Pro-pAla-OMe as a bifunctional catalyst for Michael addition between aldehydes and aromatic nitroalkenes. Considering that opposit...

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Detalles Bibliográficos
Autores: Cortes-Clerget, Margery, Jover Modrego, Jesús, Dussart, Jade, Kolodziej, Emilie, Monteil, Maelle, Migianu-Griffoni, Evelyne, Gager, Olivier, Deschamp, Julia, Lecouvey, Marc
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/142779
Acceso en línea:https://hdl.handle.net/2445/142779
Access Level:acceso abierto
Palabra clave:Reaccions d'addició
Teoria del funcional de densitat
Catàlisi
Addition reactions
Density functionals
Catalysis
Descripción
Sumario:Enamine catalysis is a widespread activation mode in the field of organocatalysis and is often encountered in bifunctional organocatalysts. We previously described H-Pro-Pro-pAla-OMe as a bifunctional catalyst for Michael addition between aldehydes and aromatic nitroalkenes. Considering that opposite selectivities were observed when compared to H-Pro-Pro-Glu-NH2, an analogue described by Wennemers, the activation mode of H-Pro-Pro-pAla-OMe was investigated through kinetic, linear effect studies, NMR analyses, and structural modifications. It appeared that only one bifunctional catalyst was involved in the catalytic cycle, by activating aldehyde through an (E)-enamine and nitroalkene through an acidic interaction. A restrained tripeptide structure was optimal in terms of distance and rigidity for better selectivities and fast reaction rates. Transition-state modeling unveiled the particular selectivity of this phosphonopeptide.