A Chiral Hydrogen Atom Abstraction Catalyst for the Enantioselective Epimerization of Meso Diols

Year: 2024

Type: article

Abstract: Hydrogen atom abstraction is an important elementary chemical process but is very difficult to carry out enantioselectively. We have developed catalysts, readily derived from the cinchona alkaloid family of natural products, which can achieve this by virtue of their chiral amine structure. The catalyst, following single-electron oxidation, desymmetrizes meso diols by selectively abstracting a hydrogen atom from one carbon center, which then regains a hydrogen atom by abstraction from a thiol. This results in an enantioselective epimerization process, forming the chiral diastereomer with high enantiomeric excess. Cyclic and acyclic 1,2-diols are compatible, as are acyclic 1,3-diols. Additionally, we demonstrate the viability of combining our approach with carbon-carbon bond formation in Giese addition. Given the increasing number of synthetic methods involving hydrogen atom transfer steps we anticipate that this work will have broad impact in the field of enantioselective radical chemistry.

Source: Apollo (University of Cambridge)

DOI: 10.17863/cam.112365

Authors: Lahdenpera, Antti, Dhankhar, Jyoti, Davies, Daniel, Lam, Nelson, Bacos, Paul, De La Vega-Hernandez, Karen, Phipps, Robert

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, AstraZeneca, Vertex Pharmaceuticals, UK Research and Innovation, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Ministerio de Ciencia e Innovación, Engineering and Physical Sciences Research Council, Agencia Estatal de Investigación, H2020 European Research Council

OpenAlex ID: W6944223111