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Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study

Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselec...

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Autores principales: Barker, Graeme, Johnson, David G, Young, Paul C, Macgregor, Stuart A, Lee, Ai-Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586480/
https://www.ncbi.nlm.nih.gov/pubmed/26248980
http://dx.doi.org/10.1002/chem.201501607
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author Barker, Graeme
Johnson, David G
Young, Paul C
Macgregor, Stuart A
Lee, Ai-Lan
author_facet Barker, Graeme
Johnson, David G
Young, Paul C
Macgregor, Stuart A
Lee, Ai-Lan
author_sort Barker, Graeme
collection PubMed
description Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au–allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive.
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spelling pubmed-45864802015-10-05 Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study Barker, Graeme Johnson, David G Young, Paul C Macgregor, Stuart A Lee, Ai-Lan Chemistry Full Papers Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au–allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive. WILEY-VCH Verlag 2015-09-21 2015-08-06 /pmc/articles/PMC4586480/ /pubmed/26248980 http://dx.doi.org/10.1002/chem.201501607 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Barker, Graeme
Johnson, David G
Young, Paul C
Macgregor, Stuart A
Lee, Ai-Lan
Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title_full Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title_fullStr Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title_full_unstemmed Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title_short Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study
title_sort chirality transfer in gold(i)-catalysed direct allylic etherifications of unactivated alcohols: experimental and computational study
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586480/
https://www.ncbi.nlm.nih.gov/pubmed/26248980
http://dx.doi.org/10.1002/chem.201501607
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