Combining Palladium and Metal Alkoxide Enables Chemoselective Access to Flexible Allyl-Pd Oxa-dipoles for Higher-Order Cycloadditions.

To address the long-standing challenge of chemoselectivity in manufacturing flexible π-allyl Pd dipoles containing extended linkers, we report a new palladium/metal alkoxide-based double activation catalysis. This catalytic system enables the successful generation of TMM oxa-1,5-dipoles from homoallylic alcohol derivatives via a conceptually distinct "locking-releasing" mechanism, wherein the shielding effect of a bulky metal alkoxide moiety is likely a key factor in the sequential process. The consequent [5 + 5] cycloaddition with cyclic vinylogous anhydrides provides direct access to valuable ten-membered lactones with a broad range of substituents at the C9-position. Moreover, chemoselectively engendering π-allyl Pd 1,7-dipoles with a fully saturated linker in the related [7 + 5] cycloaddition further demonstrates the viability of the catalytic system, affording various sp-rich 12-membered lactones.