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Diastereo‐ and Enantioselective Reductive Mannich‐type Reaction of α,β‐Unsaturated Carboxylic Acids to Ketimines: A Direct Entry to Unprotected β (2,3,3)‐Amino Acids

Stereoselective construction of unprotected β‐amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper‐catalyzed diastereo‐ and enantioselective reductive Mannich‐type reaction o...

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Detalles Bibliográficos
Autores principales: Suzuki, Hirotsugu, Kondo, Sora, Yamada, Koichiro, Matsuda, Takanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107894/
https://www.ncbi.nlm.nih.gov/pubmed/36341524
http://dx.doi.org/10.1002/chem.202202575
Descripción
Sumario:Stereoselective construction of unprotected β‐amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper‐catalyzed diastereo‐ and enantioselective reductive Mannich‐type reaction of α,β‐unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched β (2,3,3)‐amino acids with vicinal stereogenic centers. The protocol features in situ generation of transiently protected carboxylic acids by a hydrosilane and their diastereo‐ and enantioselective reductive coupling with ketimines. The synthetic utility of this process was demonstrated by a gram‐scale reaction and the transformation of β‐amino acids.