Disclosing the Intra-Catalyst Non-Covalent Interactions in Tetrahydropyran-Based Dipeptidic Catalysts

Herein, we describe how minor structural modifications to our bifunctional organocatalysts based on sugar amino acids (SAAs) can alter the network of non-covalent interactions (NCIs) within the catalyst, leading to significant changes in their catalytic activity. This is attributed to the intra-cata...

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Detalles Bibliográficos
Autores: García-Monzón, Irma, Borges-González, Jorge, Quintana Morales, Ezequiel, Fernández, Israel, Martín, Tomás
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/386616
Acceso en línea:http://hdl.handle.net/10261/386616
Access Level:acceso abierto
Palabra clave:Non-covalent interactions
organocatalysis
Michael addition
kinetics
density functional calculations
chemistry
Organic chemistry
Descripción
Sumario:Herein, we describe how minor structural modifications to our bifunctional organocatalysts based on sugar amino acids (SAAs) can alter the network of non-covalent interactions (NCIs) within the catalyst, leading to significant changes in their catalytic activity. This is attributed to the intra-catalyst NCIs, which induce conformational changes that are reflected in the transition state of the rate-determining step of the Michael addition of aldehydes to trans-β-nitrostyrenes. Through kinetic experiments, conformational analysis, and DFT calculations, we found that the presence of a methoxy group at the C4 position of the tetrahydropyran ring reduces the catalytic activity by a factor of five compared to the catalyst without the methoxy group. Additionally, we have identified the different intra-catalyst NCIs, both attractive and repulsive, that drive the conformational changes, ultimately modifying the energy levels of the transition states of the rate- and enantioselectivity-determining step of the reaction.