Lewis Acid-Base Interactions as a Racemization Strategy for the Atroposelective Synthesis of (Hetero)biaryls via Dynamic Kinetic Resolution

Due to their molecular topology, atropisomers serve as highly valuable chiral frameworks for diverse applications across academic research and industry. Despite the availability of numerous established catalytic methods for their synthesis, there is still a high demand for the development of novel a...

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Detalles Bibliográficos
Autores: Carmona, José A., Rodríguez Franco, Carlos, Fernández, Rosario, Lassaletta, José M., Hornillos, Valentín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/375343
Acceso en línea:http://hdl.handle.net/10261/375343
https://api.elsevier.com/content/abstract/scopus_id/85197715618
Access Level:acceso abierto
Palabra clave:asymmetric catalysis
axial chirality
indoles
Lewis pairs
quinolines
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Descripción
Sumario:Due to their molecular topology, atropisomers serve as highly valuable chiral frameworks for diverse applications across academic research and industry. Despite the availability of numerous established catalytic methods for their synthesis, there is still a high demand for the development of novel and resourceful strategies. In this concept article, we will detail our studies on the use of transient Lewis acid-base interactions (LABI) as a dynamization strategy for the synthesis of (hetero)biaryl atropisomers by Dynamic Kinetic Resolution (DKR). The formation of cyclic transition states, resulting from the interaction between an acidic functionality and a basic counterpart, plays a key role in facilitating racemization by substantially reducing the barrier to atropisomerization. In this scenario, we have employed transformations aimed at neutralizing the acidic nature of the Lewis acid, ultimately leading to the formation of configurationally stable enantioenriched compounds. The design of substrates and the employment of stereoselective strategies based on transition metal and biocatalysis for their resolution is detailed. Specific emphasis on the preparation of axially chiral motifs commonly found in catalysis or medicinal chemistry will also be given.