Isothiourea-catalysed enantioselective synthesis of phosphonate-functionalised β-lactones.

ABSTRACT: Despite growing interest in the reactivity and biological activity of phosphonate-containing molecules, the application of α-ketophosphonates in enantioselective formal [2 + 2] cycloadditions to generate β-lactones bearing a pendant phosphonate group remains unreported. In this manuscript, a highly diastereo- and enantioselective isothiourea-catalysed formal [2 + 2] cycloaddition of both alkyl- and aryl substituted C(1)-ammonium enolates and α-ketophosphonates is established. This strategy allows a mild, practical and scalable approach to highly enantioenriched C(3)-unsubstituted and C(3)-alkyl β-lactones bearing a phosphonate motif from their corresponding α-silyl acids, via a desilylative pathway (30 examples, up to 98%, >95 : 5 dr, >99 : 1 er). Alternatively, the use of (hetero)a

SUBMITTER: Platt FM 

PROVIDER: S-EPMC11915455 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature