Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/ Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights

2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to react with enals through oxa-Michael/Michael process cascade under the combination of iminium and enamine catalysis. These racemic hemiacetalic compounds are used as unconventional O-pronucleophiles in the initial oxa-M...

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Detalles Bibliográficos
Autores: Orue Dañobeitia, Ane, Uria Pujana, Uxue, Roca-López, David, Delso, Ignacio, Reyes Martín, Efraim, Carrillo Fernández, María Luisa, Merino, Pedro, Vicario Hernando, José Luis
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/27571
Acceso en línea:http://hdl.handle.net/10810/27571
Access Level:acceso abierto
Palabra clave:oxa-michael reaction
enantioselective total-synthesis
c-heteroatom bonds
alpha,beta-unsaturated aldehydes
asymmetric-synthesis
conjugate addition
domino reactions
diastereoselective synthesis
carbonyl-compounds
organocatalytic epoxidation
Descripción
Sumario:2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to react with enals through oxa-Michael/Michael process cascade under the combination of iminium and enamine catalysis. These racemic hemiacetalic compounds are used as unconventional O-pronucleophiles in the initial oxa-Michael reaction, also leading to the formation of a single stereoisomer under a dynamic kinetic resolution (DKR) process. Importantly, by using beta-aryl or beta-alkyl substituted alpha,beta-unsaturated substrates as initial Michael acceptors either kinetically or thermodynamically controlled diastereoisomers were formed with high stereoselection through the careful selection of the reaction conditions. Finally, a complete experimental and computational study confirmed the initially proposed DKR process during the catalytic oxa-Michael/Michael cascade reaction and also explained the kinetic/thermodynamic pathway operating in each case.