Heteroatom-Controlled Three-Component [4+3] or [3+2] Annulation of Isatin-Derived Azomethine Ylide with Azadiene: Selective Synthesis of Spirooxindole-diazepines and Density Functional Theory Studies

A novel three-component [4 + 3] annulation reaction of isatin-derived azomethine ylides with azadienes was developed for the first time to efficiently synthesize spirooxindole-diazepines incorporating a benzothiophene moiety under catalyst-free conditions. Effects of the heteroatom of azadiene on the chemoselectivity was investigated. With the use of the azadiene bearing a benzofuran moiety as a substrate, the dominant reaction pathway was changed to an alpha-[3 + 2] annulation. When azadiene bearing an indenone moiety was used, a distinct gamma-[3 + 2] annulation was observed. Density functional theory calculations revealed that a delicate balance between kinetic accessibility and the thermodynamic driving force controlled the competition of different annulation reactions.