Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Lin Zhang; Ken Yamazaki; Jamie A. Leitch; Ruben Manzano; Victoria A.M. Atkinson; Trevor A. Hamlin; Darren J. Dixon

doi:10.1039/d0sc02878a

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Lin Zhang, Ken Yamazaki, Jamie A. Leitch, Ruben Manzano, Victoria A.M. Atkinson, Trevor A. Hamlin, Darren J. Dixon^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations. This journal is

Original language	English
Pages (from-to)	7444-7450
Number of pages	7
Journal	Chemical Science
Volume	11
Issue number	28
Early online date	24 Jun 2020
DOIs	https://doi.org/10.1039/d0sc02878a
Publication status	Published - 28 Jun 2020

Funding

L. Z. is supported by the funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement no. 751281-H2020-MSCA-IF-2016. K. Y. thanks the Honjo International Scholarship Foundation for funding. This work was supported by The Netherlands Organization for Scientic Research (NWO). J. A. L. thanks the Leverhulme Trust (RPG-2017-069) for a research fellowship. R. M. thanks the EU commission for IEF (PIEF-GA-2013-627232). We thank Heyao Shi for X-ray structure determination and Dr Amber L. Thompson and Dr Kirsten E. Christensen (Oxford Chemical Crystallography Service) for X-ray mentoring and help.

Funders	Funder number
Netherlands Organization for Scientic Research
H2020 Marie Skłodowska-Curie Actions	751281-H2020-MSCA-IF-2016
Leverhulme Trust	RPG-2017-069
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Honjo International Scholarship Foundation
Horizon 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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abstract = "The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations. This journal is ",

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AU - Zhang, Lin

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AU - Leitch, Jamie A.

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AU - Atkinson, Victoria A.M.

AU - Hamlin, Trevor A.

AU - Dixon, Darren J.

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AB - The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations. This journal is

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Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Abstract

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CCDC 2000237: Experimental Crystal Structure Determination

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Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Abstract

Funding

UN SDGs

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CCDC 2000237: Experimental Crystal Structure Determination

Cite this