Abstract

Macrolactones are commonly found in natural products and pharmaceuticals. Herein, we present Pd-catalyzed [7 + 5] and higher-order annulations between unprecedented oxa-1,n-dipoles (n = 7-9) with active enol lactones. This protocol enables the rapid synthesis of complex 12 to 15-membered lactones bearing internal E-alkenes. Density functional theory calculations have revealed the favorable reaction pathway and identified coordination interactions between active enol lactones and palladium centers of π-allyl dipole species as key factors in manipulating these dipoles in annulations.

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