ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
4 files

Dual Catalytic Enantioselective Desymmetrization of Allene-Tethered Cyclohexanones

preprint
submitted on 21.05.2020, 13:07 and posted on 22.05.2020, 05:09 by Lin Zhang, Ken Yamazaki, Jamie Leitch, Ruben Manzano, Victoria Atkinson, Trevor Hamlin, Darren J. Dixon

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.

Funding

Horizon 2020

Leverhulme Trust

Honjo International Scholarship Foundation

Netherlands Organization for Scientific Research (NWO)

History

Email Address of Submitting Author

jamie.leitch@chem.ox.ac.uk

Institution

University of Oxford

Country

United Kingdom

ORCID For Submitting Author

0000-0001-6997-184X

Declaration of Conflict of Interest

No conflict of interest