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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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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
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author Suzuki, Hirotsugu
Kondo, Sora
Yamada, Koichiro
Matsuda, Takanori
author_facet Suzuki, Hirotsugu
Kondo, Sora
Yamada, Koichiro
Matsuda, Takanori
author_sort Suzuki, Hirotsugu
collection PubMed
description 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.
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spelling pubmed-101078942023-04-18 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 Suzuki, Hirotsugu Kondo, Sora Yamada, Koichiro Matsuda, Takanori Chemistry Research Articles 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. John Wiley and Sons Inc. 2022-12-08 2023-01-18 /pmc/articles/PMC10107894/ /pubmed/36341524 http://dx.doi.org/10.1002/chem.202202575 Text en © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Suzuki, Hirotsugu
Kondo, Sora
Yamada, Koichiro
Matsuda, Takanori
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Articles
url 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
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