Ir-catalyzed asymmetric formal (3 + 2) cycloaddition of esters with vinylcyclopropanes

Chiral polysubstituted tetrahydrofurans are key motifs in natural products and pharmaceuticals, and the stereoselective assembly of these architectures is of great importance. Herein, we report an Ir-catalyzed asymmetric formal (3 + 2) cycloaddition of activated esters with donor-acceptor vinylcyclopropanes, providing rapid access to diverse tetrahydrofuran scaffolds with excellent enantio- and <i>Z</i>/<i>E</i>-selectivity (up to >99% ee and >20 : 1 <i>Z</i>/<i>E</i>) under mild conditions. The method displays broad substrate scope, including pharmaceutically relevant esters, and is amenable to gram-scale synthesis and downstream functionalization. Mechanistic studies indicate the involvement of acylammonium and zwitterionic π-allyl-Ir intermediates, offering insight into the observed stereocontrol. This strategy directly leverages ester carbonyls in cycloaddition chemistry, establishing a versatile platform for the stereoselective construction of biologically relevant tetrahydrofuran frameworks.