Phenolic Activation in Chiral Brønsted Acid-Catalyzed Intramolecular α‑Amidoalkylation Reactions for the Synthesis of Fused Isoquinolines
An organolithium addition−intramolecular α- amidoalkylation sequence on N-phenethylimides has been developed for the synthesis of fused tetrahydroisoquinoline systems using 1,1′-bi-2-naphthol (binol)-derived Brønsted acids. This transformation is the first in which activated benzene derivatives are...
| Autores: | , , |
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| 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:10810/64227 |
| Acceso en línea: | http://hdl.handle.net/10810/64227 |
| Access Level: | acceso abierto |
| Palabra clave: | organocatalysis Chiral Bronsted acid asymmetric catalysisi acyliminium ions alkaloids |
| Sumario: | An organolithium addition−intramolecular α- amidoalkylation sequence on N-phenethylimides has been developed for the synthesis of fused tetrahydroisoquinoline systems using 1,1′-bi-2-naphthol (binol)-derived Brønsted acids. This transformation is the first in which activated benzene derivatives are used as internal nucleophiles, instead of electron-rich heteroaromatics, generating a quaternary stereocenter. Phenolic substitution on the aromatic ring of the phenethylamino moiety and the use of binol-derived N-triflylphosphoramides as catalysts are determinants to achieve reasonable levels of enantioselection, that is, up to 75% enantiomeric excess, in the α-amidoalkylation step. The procedure is complementary to the intermolecular α-amidoalkylation process, as opposite enantiomers are formed, and to the Pictet− Spengler cyclization, which allows the formation of tertiary stereocenters |
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