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A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres

The catalytic enantioselective synthesis of densely functionalised organic molecules containing all-carbon quaternary stereocentres is a challenge to modern chemical methodology research. The catalytically controlled asymmetric α-alkylation of ketones represents another difficult task and has been o...

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Autores principales: Streuff, Jan, White, David E., Virgil, Scott C., Stoltz, Brian M.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917108/
https://www.ncbi.nlm.nih.gov/pubmed/20697457
http://dx.doi.org/10.1038/nchem.518
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author Streuff, Jan
White, David E.
Virgil, Scott C.
Stoltz, Brian M.
author_facet Streuff, Jan
White, David E.
Virgil, Scott C.
Stoltz, Brian M.
author_sort Streuff, Jan
collection PubMed
description The catalytic enantioselective synthesis of densely functionalised organic molecules containing all-carbon quaternary stereocentres is a challenge to modern chemical methodology research. The catalytically controlled asymmetric α-alkylation of ketones represents another difficult task and has been of major interest to our and other research groups in the past. We now report a palladium-catalyzed enantioselective process that addresses both problems at once and allows the installation of vicinal all-carbon quaternary and tertiary stereocentres at the α-carbon of a ketone in a single step. This multiple bond forming process is carried out on readily available β-ketoester starting materials and proceeds via conjugate addition of an in situ-generated palladium enolate to activated Michael acceptors. In other words, the CO(2)-moiety of the substrate is displaced by a C-C fragment in an asymmetric cut-and-paste reaction. The products are obtained in high yield, diastereomeric ratio, and enantiomeric excess.
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spelling pubmed-29171082010-09-01 A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres Streuff, Jan White, David E. Virgil, Scott C. Stoltz, Brian M. Nat Chem Article The catalytic enantioselective synthesis of densely functionalised organic molecules containing all-carbon quaternary stereocentres is a challenge to modern chemical methodology research. The catalytically controlled asymmetric α-alkylation of ketones represents another difficult task and has been of major interest to our and other research groups in the past. We now report a palladium-catalyzed enantioselective process that addresses both problems at once and allows the installation of vicinal all-carbon quaternary and tertiary stereocentres at the α-carbon of a ketone in a single step. This multiple bond forming process is carried out on readily available β-ketoester starting materials and proceeds via conjugate addition of an in situ-generated palladium enolate to activated Michael acceptors. In other words, the CO(2)-moiety of the substrate is displaced by a C-C fragment in an asymmetric cut-and-paste reaction. The products are obtained in high yield, diastereomeric ratio, and enantiomeric excess. 2010-03 /pmc/articles/PMC2917108/ /pubmed/20697457 http://dx.doi.org/10.1038/nchem.518 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Streuff, Jan
White, David E.
Virgil, Scott C.
Stoltz, Brian M.
A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title_full A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title_fullStr A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title_full_unstemmed A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title_short A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
title_sort palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917108/
https://www.ncbi.nlm.nih.gov/pubmed/20697457
http://dx.doi.org/10.1038/nchem.518
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