Iridium-catalyzed regio- and diastereoselective synthesis of C-substituted piperazines

Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines...

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Detalles Bibliográficos
Autores: Tarifa, Luis Miguel, Río, M. Pilar del, Asensio, Laura, López, José A., Ciriano, Miguel A., Geer, Ana M., Tejel, Cristina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/290330
Acceso en línea:http://hdl.handle.net/10261/290330
Access Level:acceso abierto
Palabra clave:Piperazines
Iridium
Homogeneous catalysis
[3 + 3]-cycloadditions
Imines
Trimethylamine N-oxide
Descripción
Sumario:Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines. This 100% atom-economic process allows the selective formation of a sole diastereoisomer, a broad substrate scope, and a good functional group tolerance employing a bench-stable iridium catalyst under mild reaction conditions. Key to the success is the addition of N-oxides to the reaction mixture, as they notably enhance the catalytic activity and selectivity.