Enantioselective inverse-electron demand Aza-Diels-Alder reaction: ipso,α-selectivity of silyl dienol ethers

A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenter...

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Detalles Bibliográficos
Autores: Laina-Martín, Víctor, Humbrías-Martín, Jorge, Mas Ballesté, Rubén, Fernández-Salas, Jose A., Alemán Lara, José Julián
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/700286
Acceso en línea:http://hdl.handle.net/10486/700286
https://dx.doi.org/10.1021/acscatal.1c03390
Access Level:acceso abierto
Palabra clave:Diels−Alder
Benzofuran derivatives
Bifunctional catalysis
Hydrogen-bonding activation
Organocatalysis
Squaramide
Química
Descripción
Sumario:A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner, as even the hemiaminal center is completely stereocontrolled. Density functional theory (DFT) calculations support that the hydrogen-bond donor-based bifunctional organocatalyst selectively triggers the reaction through the ipso,α-position of the dienophile, in contrast to the reactivity observed for dienolates in situ generated from β,γ-unsaturated derivatives. Moreover, the calculations have clarified the mechanism of the reaction and the ability of the hydrogen-bond donor core to hydrolyze selectively theEisomer of the dienol ether. Furthermore, to demonstrate the applicability of silyl enol ethers as nucleophiles in the asymmetric synthesis of interesting benzofuran-fused derivatives, the catalytic system has also been implemented for the highly efficient installation of an aromatic ring in the piperidine adducts