Heteroatom-Controlled\nThree-Component [4 + 3] or [3\n+ 2] Annulation of Isatin-Derived Azomethine Ylide with Azadiene:\nSelective Synthesis of Spirooxindole-diazepines and Density Functional\nTheory Studies

A novel\nthree-component [4 + 3] annulation reaction of isatin-derived\nazomethine ylides with azadienes was developed for the first time\nto efficiently synthesize spirooxindole-diazepines incorporating a\nbenzothiophene moiety under catalyst-free conditions. Effects of the\nheteroatom of azadiene on the chemoselectivity was investigated. With\nthe use of the azadiene bearing a benzofuran moiety as a substrate,\nthe dominant reaction pathway was changed to an α-[3 + 2] annulation.\nWhen azadiene bearing an indenone moiety was used, a distinct γ-[3\n+ 2] annulation was observed. Density functional theory calculations\nrevealed that a delicate balance between kinetic accessibility and\nthe thermodynamic driving force controlled the competition of different\nannulation reactions.