Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols

Experimental and Computational Study

Graeme Barker, David G Johnson, Paul C Young, Stuart A Macgregor, Ai-Lan Lee

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalChemistry - A European Journal
DOIs
Publication statusPublished - 6 Aug 2015

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@article{28216603208f4b579c39d7ab6321d873,
title = "Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study",
abstract = "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.",
author = "Graeme Barker and Johnson, {David G} and Young, {Paul C} and Macgregor, {Stuart A} and Ai-Lan Lee",
note = "{"}We thank the EPSRC (EP/K00736X/1) and EPSRC DTA studentship (P.C.Y.) for funding. Mass spectrometry data was acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University{"}",
year = "2015",
month = "8",
day = "6",
doi = "10.1002/chem.201501607",
language = "English",
journal = "Chemistry - A European Journal",
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publisher = "Wiley-VCH Verlag",

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TY - JOUR

T1 - Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols

T2 - Experimental and Computational Study

AU - Barker, Graeme

AU - Johnson, David G

AU - Young, Paul C

AU - Macgregor, Stuart A

AU - Lee, Ai-Lan

N1 - "We thank the EPSRC (EP/K00736X/1) and EPSRC DTA studentship (P.C.Y.) for funding. Mass spectrometry data was acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University"

PY - 2015/8/6

Y1 - 2015/8/6

N2 - 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.

AB - 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.

U2 - 10.1002/chem.201501607

DO - 10.1002/chem.201501607

M3 - Article

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

ER -