Palladium-Catalyzed [7 + 5] and Higher-Order Annulations\nof Oxa-1,n-dipoles: Synthesis of 12- to 15-Membered Lactones

Macrolactones are commonly found\nin natural products and pharmaceuticals.\nHerein, we present Pd-catalyzed [7 + 5] and higher-order annulations\nbetween unprecedented oxa-1,n-dipoles (n = 7–9) with active\nenol lactones. This protocol enables the rapid synthesis of complex\n12 to 15-membered lactones bearing internal <i>E</i>-alkenes.\nDensity functional theory calculations have revealed the favorable\nreaction pathway and identified coordination interactions between\nactive enol lactones and palladium centers of π-allyl dipole\nspecies as key factors in manipulating these dipoles in annulations.