Palladium-Catalyzed Isomerization/Hydrocarbonylation of Electron-Deficient Alkenes for the Construction of Lactones and Lactams

An efficient palladium-catalyzed isomerization/hydrocarbonylation of electron-deficient alkenes was developed, affording a variety of benzofuran-2(3<i>H</i>)-ones, dihydrofuran-2(3<i>H</i>)-ones, indolin-2-ones, and isochroman-3-ones in high yields. The reaction exhibits excellent regioselectivity, high atom economy, and a broad range of substrates. The late-stage modification of bioactive molecules and scaled-up reaction demonstrated the practicability of this methodology. Furthermore, the method was employed as the key step for the synthesis of an insulin degrading enzyme (IDE) activator.