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New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries

Ligands are essential for controlling the reactivity and selectivity of transition metal-catalyzed reactions. Access to large phosphine ligand libraries has become an essential tool for the application of metal-catalyzed reactions industrially, but these existing libraries are not well suited to new...

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Autores principales: Hansen, Eric C., Pedro, Dylan J., Wotal, Alexander C., Gower, Nicholas J., Nelson, Jade D., Caron, Stephane, Weix, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123601/
https://www.ncbi.nlm.nih.gov/pubmed/27874864
http://dx.doi.org/10.1038/nchem.2587
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author Hansen, Eric C.
Pedro, Dylan J.
Wotal, Alexander C.
Gower, Nicholas J.
Nelson, Jade D.
Caron, Stephane
Weix, Daniel J.
author_facet Hansen, Eric C.
Pedro, Dylan J.
Wotal, Alexander C.
Gower, Nicholas J.
Nelson, Jade D.
Caron, Stephane
Weix, Daniel J.
author_sort Hansen, Eric C.
collection PubMed
description Ligands are essential for controlling the reactivity and selectivity of transition metal-catalyzed reactions. Access to large phosphine ligand libraries has become an essential tool for the application of metal-catalyzed reactions industrially, but these existing libraries are not well suited to new catalytic methods based on non-precious metals (i.e., Ni, Cu, Fe). The development of the requisite nitrogen- and oxygen-based ligand libraries lags far behind phosphines and the development of new libraries is anticipated to be time consuming. Here we show that this process can be dramatically accelerated by mining a typical pharmaceutical compound library that is rich in heterocycles for new ligands. Using this approach, we were able to screen a structurally diverse set of compounds with minimal synthetic effort and identify several new ligand classes for nickel-catalyzed cross-electrophile coupling. These new ligands gave improved yields for challenging cross-couplings of pharmaceutically relevant substrates compared to previously published ligands.
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spelling pubmed-51236012017-02-08 New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries Hansen, Eric C. Pedro, Dylan J. Wotal, Alexander C. Gower, Nicholas J. Nelson, Jade D. Caron, Stephane Weix, Daniel J. Nat Chem Article Ligands are essential for controlling the reactivity and selectivity of transition metal-catalyzed reactions. Access to large phosphine ligand libraries has become an essential tool for the application of metal-catalyzed reactions industrially, but these existing libraries are not well suited to new catalytic methods based on non-precious metals (i.e., Ni, Cu, Fe). The development of the requisite nitrogen- and oxygen-based ligand libraries lags far behind phosphines and the development of new libraries is anticipated to be time consuming. Here we show that this process can be dramatically accelerated by mining a typical pharmaceutical compound library that is rich in heterocycles for new ligands. Using this approach, we were able to screen a structurally diverse set of compounds with minimal synthetic effort and identify several new ligand classes for nickel-catalyzed cross-electrophile coupling. These new ligands gave improved yields for challenging cross-couplings of pharmaceutically relevant substrates compared to previously published ligands. 2016-08-08 2016-12 /pmc/articles/PMC5123601/ /pubmed/27874864 http://dx.doi.org/10.1038/nchem.2587 Text en Reprints and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) . Users may view, print, copy, and download 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
Hansen, Eric C.
Pedro, Dylan J.
Wotal, Alexander C.
Gower, Nicholas J.
Nelson, Jade D.
Caron, Stephane
Weix, Daniel J.
New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title_full New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title_fullStr New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title_full_unstemmed New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title_short New Ligands for Nickel Catalysis from Diverse Pharmaceutical Heterocycle Libraries
title_sort new ligands for nickel catalysis from diverse pharmaceutical heterocycle libraries
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123601/
https://www.ncbi.nlm.nih.gov/pubmed/27874864
http://dx.doi.org/10.1038/nchem.2587
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