Dynamic Kinetic Resolution Allows Control of Remote Stereochemistry in Asymmetric Hydrogen Borrowing Alkylation
A catalytic asymmetric method for the synthesis of γ-substituted ketones via hydrogen borrowing alkylation of both racemic linear precursors and 1,5-diols is described. The base mediated racemization of an intermediate cyclohexenone to facilitates a dynamic kinetic resolution, affording highly enantioenriched cyclohexanes in excellent yields, which could be further functionalized by removal of the Ph* group. DFT modelling revealed the mode of enantioinduction to be a stepwise process comprising of a hydride transfer and a coordination change to a π-allylic enolate complex with the iridium catalyst.
Authors
- Kirsten E. Christensen (ORCID: https://orcid.org/0000-0003-1683-2066)
- Jessica L. Crompton (ORCID: https://orcid.org/0000-0003-2648-5686)
- Francisco O. Battiti (ORCID: https://orcid.org/0000-0002-5949-6413)
- Fernanda Duarte (ORCID: https://orcid.org/0000-0002-6062-8209)
- Mostafa M. Amer (ORCID: https://orcid.org/0000-0001-6234-2311)
- Daniella Cheang (ORCID: https://orcid.org/0000-0001-7046-3295)
- Timothy J. Donohoe (ORCID: https://orcid.org/0000-0001-7088-6626)
- Bastian Bjerkem Skjelstad (ORCID: https://orcid.org/0000-0002-9769-6459)
- Peter Barton
Institutions
- AstraZeneca (United Kingdom) (GB)
- Mansfield University (US)
- Oxford Research Group (GB)
- University of Oxford (GB)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1002/anie.202424959
- Citations
- 3
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Pfizer
- AstraZeneca
- Diamond Light Source
- UK Research and Innovation
- Royal Commission for the Exhibition of 1851
- National Institutes of Health
- Defence Science and Technology Laboratory
- Engineering and Physical Sciences Research Council
- Defence Science and Technology Group
- H2020 Marie Skłodowska-Curie Actions