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.