Synthesis of Imidazopyridine- and Indole-Fused Azepinones via an Unusual Friedel–Crafts Alkylation of Chloroacetylated GBB Adducts

A new Friedel-Crafts-type reaction involving the formation and ring expansion of spiro-β-lactam is discovered in the synthesis of imidazopyridine- and indole-fused azepinones. The Groebke-Blackburn-Bienaymé (GBB) reaction adducts undergo N-chloroacylation and Friedel-Crafts alkylation, which leads to polycyclic products in good yields. The DFT calculation indicates that in the Friedel-Crafts reaction spiralization at C-11 is kinetically more favorable than that directly at C-2. It is a novel rearrangement process for the synthesis of biologically interesting azepinone derivatives.