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 α-[3 + 2] annulation.
When azadiene bearing an indenone moiety was used, a distinct γ-[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.