Despite growing interest in the reactivity and biological activity of phosphonate-containing molecules, the application of α‑ketophosphonates in enantioselective [2+2] cycloadditions to generate β-lactones bearing a pendant phosphonate group remains unreported. In this manuscript, a highly diastereo- and enantioselective isothiourea-catalysed [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)arylacetic acids allows the preparation of C(3)-(hetero)aryl β‑lactones to be accessed in high yields and stereocontrol (19 examples, up to 98%, 95:5 dr, 99:1 er).
