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

AIMMS

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
H2020 Marie Skłodowska-Curie Actions
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Horizon 2020 Framework Programme
Honjo International Scholarship Foundation
European Commission
Netherlands Organization for Scientic Research
Horizon 2020
Seventh Framework Programme	751281, 627232
Leverhulme Trust	RPG-2017-069

UN SDGs

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

SDG 6 Clean Water and Sanitation

Access to Document

10.1039/d0sc02878a

Persistent URL (handle)

Persistent link

Cite this

@article{5f4d4e23dcfc4dc6bc0b316541dd2998,

title = "Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones",

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 ",

author = "Lin Zhang and Ken Yamazaki and Leitch, \{Jamie A.\} and Ruben Manzano and Atkinson, \{Victoria A.M.\} and Hamlin, \{Trevor A.\} and Dixon, \{Darren J.\}",

year = "2020",

month = jun,

day = "28",

doi = "10.1039/d0sc02878a",

language = "English",

volume = "11",

pages = "7444--7450",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "28",

}

TY - JOUR

T1 - Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

AU - Zhang, Lin

AU - Yamazaki, Ken

AU - Leitch, Jamie A.

AU - Manzano, Ruben

AU - Atkinson, Victoria A.M.

AU - Hamlin, Trevor A.

AU - Dixon, Darren J.

PY - 2020/6/28

Y1 - 2020/6/28

N2 - 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

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

UR - https://www.scopus.com/pages/publications/85088699018

UR - https://www.scopus.com/pages/publications/85088699018#tab=citedBy

U2 - 10.1039/d0sc02878a

DO - 10.1039/d0sc02878a

M3 - Article

AN - SCOPUS:85088699018

SN - 2041-6520

VL - 11

SP - 7444

EP - 7450

JO - Chemical Science

JF - Chemical Science

IS - 28

ER -

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Abstract

Funding

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

CCDC 2000237: Experimental Crystal Structure Determination

Cite this

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones

Abstract

Funding

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Datasets

CCDC 2000237: Experimental Crystal Structure Determination

Cite this