Catalytic Enantioselective Nucleophilic Desymmetrisation of Phosphonate Esters

Abstract

Compounds containing one or more stereogenic phosphorous atoms in the P(V) oxidation state are important to chemistry, biology and medicine. 1 These include marketed antiviral drugs such as Tenofovir alafenamide and Remdesivir, 2 an effective treatment for Ebola which has also recently been approved for use against SARS-CoV-2 in the US.Existing approaches for the stereoselective synthesis of P-stereogenic centers, while elegant, remain mostly diastereoselective, with catalytic enantioselective approaches remaining limited in application. Accordingly, conceptually novel, broad-scope, catalytic strategies for the efficient stereoselective synthesis of diverse stereogenic P(V) containing compounds remain essential. 3

Enantioselective Synthesis of Versatile Stereogenic-at-P(V) Building Blocks via Hydrogen-Bond-Donor Catalysis

“…An alternative approach was demonstrated by Miller and co-workers in the catalytic, stereodivergent synthesis of P-stereogenic oligonucleotides from phosphoramidites via chiral phosphoric acid catalysis (24). Finally, in work that appeared as this study was being completed, Dixon and co-workers reported a catalytic, enantioselective desymmetrization of diaryl phosphonate esters by substitution with orthosubstituted phenols (25). While high levels of stereoselectivity were achieved in these catalytic, nucleophilic substitution reactions, each is limited to a narrow class of nucleophiles that are not further displaced.…”

Enantioselective Arbuzov Reaction Enabled by Catalytic Ion-Pair Reorganization

“…stereoselective construction of P-stereogenic compounds(17,18). https://doi.org/10.26434/chemrxiv-2024-1ph89 ORCID: https://orcid.org/0000-0001-7952-3661 Content not peer-reviewed by ChemRxiv.…”