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Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols

The combination of small‐molecule catalysis and enzyme catalysis represents an underexploited area of research with huge potential in asymmetric synthetic chemistry due to both compatibility of reaction conditions and complementary reactivity. Herein, we describe the telescopic synthesis of chiral n...

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Autores principales: Ascaso‐Alegre, Christian, Herrera, Raquel P., Mangas‐Sánchez, Juan
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/PMC9826084/
https://www.ncbi.nlm.nih.gov/pubmed/35983936
http://dx.doi.org/10.1002/anie.202209159
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author Ascaso‐Alegre, Christian
Herrera, Raquel P.
Mangas‐Sánchez, Juan
author_facet Ascaso‐Alegre, Christian
Herrera, Raquel P.
Mangas‐Sánchez, Juan
author_sort Ascaso‐Alegre, Christian
collection PubMed
description The combination of small‐molecule catalysis and enzyme catalysis represents an underexploited area of research with huge potential in asymmetric synthetic chemistry due to both compatibility of reaction conditions and complementary reactivity. Herein, we describe the telescopic synthesis of chiral nitro alcohols starting from commercially available benzaldehyde derivatives through the one‐pot three‐step chemoenzymatic cascade combination of a Wittig reaction, chiral‐thiourea‐catalysed asymmetric conjugate addition, and ketoreductase‐mediated reduction to access the corresponding target compounds in moderate to excellent overall isolated yields (36–80 %) and high diastereomeric and enantiomeric ratios (up to >97 : 3). This represents the first example of the combination of an organocatalysed asymmetric conjugate addition via iminium ion activation and a bioreduction step catalysed by ketoreductases.
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spelling pubmed-98260842023-01-09 Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols Ascaso‐Alegre, Christian Herrera, Raquel P. Mangas‐Sánchez, Juan Angew Chem Int Ed Engl Communications The combination of small‐molecule catalysis and enzyme catalysis represents an underexploited area of research with huge potential in asymmetric synthetic chemistry due to both compatibility of reaction conditions and complementary reactivity. Herein, we describe the telescopic synthesis of chiral nitro alcohols starting from commercially available benzaldehyde derivatives through the one‐pot three‐step chemoenzymatic cascade combination of a Wittig reaction, chiral‐thiourea‐catalysed asymmetric conjugate addition, and ketoreductase‐mediated reduction to access the corresponding target compounds in moderate to excellent overall isolated yields (36–80 %) and high diastereomeric and enantiomeric ratios (up to >97 : 3). This represents the first example of the combination of an organocatalysed asymmetric conjugate addition via iminium ion activation and a bioreduction step catalysed by ketoreductases. John Wiley and Sons Inc. 2022-09-05 2022-10-04 /pmc/articles/PMC9826084/ /pubmed/35983936 http://dx.doi.org/10.1002/anie.202209159 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Communications
Ascaso‐Alegre, Christian
Herrera, Raquel P.
Mangas‐Sánchez, Juan
Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title_full Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title_fullStr Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title_full_unstemmed Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title_short Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols
title_sort stereoselective three‐step one‐pot cascade combining amino‐ and biocatalysis to access chiral γ‐nitro alcohols
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826084/
https://www.ncbi.nlm.nih.gov/pubmed/35983936
http://dx.doi.org/10.1002/anie.202209159
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