Clarke, Paul Andrew orcid.org/0000-0003-3952-359X, Ermanis, Kristaps, Hsiao, Yin-Ting et al. (2 more authors) (2017) The Stereodivergent Formation of 2,6-cis and 2,6-trans-Tetrahydropyrans: Experimental and Computational Investigation of the Mechanism of a Thioester Oxy-Michael Cyclization. Chemical Science. C6SC03478K. pp. 482-490. ISSN 2041-6539
Abstract
The origins of the stereodivergence in the thioester oxy-Michael cyclization for the formation of 4-hydroxy-2,6-cis- or 2,6-trans-substituted tetrahydropyran rings under different conditions was investigated both computationally and experimentally. Synthetic studies showed that the 4-hydroxyl group was essential for stereodivergence. When the 4-hydroxyl group was present, TBAF-mediated conditions gave the 2,6-trans-tetrahydropyran and trifluoroacetic acid-mediated conditions gave the 2,6-cis-tetrahydropyran. This stereodivergence vanished when the hydroxyl group was removed or protected. Computational studies revealed that: (i) the trifluoroacetic acid catalysed formation of 2,6-cis-tetrahydropyrans was mediated by a trifluoroacetate-hydroxonium bridge and proceeded via a chair-like transition state; (ii) the TBAF-mediated formation of 2,6-trans-tetrahydropyrans proceeded via a boat-like transition state, where the 4-hydroxyl group formed a crucial hydrogen bond to the cyclizing alkoxide; (iii) both reactions are under kinetic control. The utility of this stereodivergent approach for the formation of 4-hydroxy-2,6-substituted tetrahydropyran rings has been demonstrated by the total syntheses of the anti-osteoporotic natural products diospongin A and B
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 08 Sep 2016 09:51 |
Last Modified: | 16 Oct 2024 13:14 |
Published Version: | https://doi.org/10.1039/C6SC03478K |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1039/C6SC03478K |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104199 |
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