Synthesis of racemic δ,δ-dimethylproline derivatives

A versatile methodology for the preparation of racemic δ,δ- dimethylproline derivatives has been developed. Methyl N-Boc-δ,δ- dimethylprolinate was synthesized from a β-amino acid in six steps and 55 % overall yield. The route is amenable to the preparation of a broad range of δ,δ-disubstituted prol...

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Detalles Bibliográficos
Autores: Rodríguez-Díaz, Isabel, Calaza, M. Isabel, Cativiela, Carlos
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/111481
Acceso en línea:http://hdl.handle.net/10261/111481
Access Level:acceso abierto
Palabra clave:Synthetic methods
Proline analogues
Nitrogen heterocycles
Regioselectivity
Amino acids
Descripción
Sumario:A versatile methodology for the preparation of racemic δ,δ- dimethylproline derivatives has been developed. Methyl N-Boc-δ,δ- dimethylprolinate was synthesized from a β-amino acid in six steps and 55 % overall yield. The route is amenable to the preparation of a broad range of δ,δ-disubstituted prolines by starting with the adequate β-amino acids. In addition, one of the intermediate compounds in the synthetic route has been used for the preparation of a δ,δ- dimethylproline derivative that is substituted at the β-position with a phenyl group. This has been achieved by coupling phenylboronic acid with a regioselectively generated vinyl triflate followed by a stereoselective hydrogenation. δ,δ-Dimethylproline derivatives have been efficiently synthesized by employing a β-amino acid as the starting material. The methodology is amenable to the preparation of other δ,δ- disubstituted prolines. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.