Sulfoximine Aided δ-1,1-Cascade Heterocyclization of Unactivated Alkenes

This study demonstrates a palladium-catalyzed δ-annulative 1,1-difunctionalization of unactivated alkenes through a combination of C(alkenyl)–H activation, oxidative addition/reductive elimination, and syn-nucleometalation. The 2-pyridyl-methyl sulfoximine (MPyS) bidentate directing group, together with the 2-hydroxy-5-methylpyridine ligand, is crucial for making the transformation feasible under mild conditions. The process enables the formation of C–C/C–O bonds in a single operation, as evidenced by the use of bifunctional reagents (BFRs) of the 2-iodobenzamide or 2-iodobenzoic acid series. Notably, the de novo synthesis of α-branched isobenzofuran-1(3H)-imine and phthalides underscores its practical utility. Mechanistic studies and DFT computations uncover the intricacies of the catalytic cycle. Additionally, this method provides direct access to the synthesis of a monoamine oxidase A inhibitor.