Transition-Metal-Based Dearomatization Strategy for the Synthesis of Functionalized cis-Tetrahydro-2-Oxindoles

cis-Tetrahydro-2-oxindoles are valuable scaffolds in medicinal chemistry. Herein, we report a transition-metal-mediated dearomatization strategy to access these compounds. The process begins with the coordination of a phenyl sulfone by a tungsten complex designed to bind two carbons of the phenyl ring, rendering it dearomatized. This is followed by protonation of the η(2)-bound arene followed by the addition of an ester nucleophile. The resulting η(2)-diene complex then undergoes a second protonation in the ring, and a primary amine is introduced. Dihydro-2-oxindole complexes form spontaneously through the construction of a γ-lactam and the elimination of a sulfinic acid. Dihydro-2-oxindoles are practically unknownpresumably owing to their ability to form indolinesbut coordination to tungsten stabilizes these intermediates. The terminal position of the coordinated diene (C4 of the 2-oxindole core) can then be protonated to generate an η(2)-allyl complex, which undergoes nucleophilic addition with C-, N-, or S-type nucleophiles to form the corresponding tetrahydro-2-oxindole complexes. Finally, the organic ligand is obtained through the oxidative decomplexation of the metal. This methodology provides a modular approach for accessing 1,2,5-functionalized cis-2-oxindole compounds.