title: Chiral Brønsted Acid-Catalyzed Enantioselective α-Amidoalkylation Reactions: A Joint Experimental and Predictive Study.
abstract: Enamides with a free NH group have been evaluated as nucleophiles in chiral Brønsted acid-catalyzed enantioselective α-amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure-reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)-QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long-term empirical investigation.
authors.affiliation: Departamento de Química Orgánica II Facultad de Ciencia y Tecnología Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Apdo. 644 48080 Bilbao Spain.
authors.forename: Eider
authors.identifier: 0000-0003-1750-0311
authors.initials: E
authors.lastname: Aranzamendi
authors.affiliation: Departamento de Química Orgánica II Facultad de Ciencia y Tecnología Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Apdo. 644 48080 Bilbao Spain.
authors.forename: Sonia
authors.identifier: 0000-0003-2601-5959
authors.initials: S
authors.lastname: Arrasate
authors.affiliation: Departamento de Química Orgánica II Facultad de Ciencia y Tecnología Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Apdo. 644 48080 Bilbao Spain.
authors.forename: Nuria
authors.identifier: 0000-0003-3079-6380
authors.initials: N
authors.lastname: Sotomayor
authors.affiliation: Departamento de Química Orgánica II Facultad de Ciencia y Tecnología Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Apdo. 644 48080 Bilbao Spain; IKERBASQUE Basque Foundation for Science 48080 Bilbao Spain.
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
authors.affiliation: Departamento de Química Orgánica II Facultad de Ciencia y Tecnología Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Apdo. 644 48080 Bilbao Spain.
authors.forename: Esther
authors.identifier: 0000-0001-8624-6842
authors.initials: E
authors.lastname: Lete
keywords: amidoalkylation; asymmetric catalysis; cheminformatics; chiral Brønsted acids; quantitative structure–reactivity relationships