Regioselective [3 + 2] Annulation of Multisubstituted N -Allenamides: A Palladium-Catalyzed Heck/Tsuji–Trost Cascade Approach

A palladium-catalyzed Heck/Tsuji–Trost cascade has been established for the regioselective [3 + 2] annulation of multisubstituted N -allenamides with ortho -iodoaniline and ortho -iodophenol derivatives. Notably, this approach proceeds via selective γ-attack on multisubstituted N -allenamides, delivering distal bond insertion products, in contrast to previously reported reactions involving proximal bond insertion of simple N -allenamides. This method enables the efficient synthesis of enamide-tagged indolines and dihydrobenzofurans bearing quaternary carbon centers in good to excellent yields with exclusive distal regioselectivity and broad functional group compatibility. Density functional theory calculations provide a clear rationale for the observed regio- and geometric selectivity.