Mechanistic Insights into the Stereocontrolled Synthesis of Hexahydropyrrolo[2,3-b]indoles by Electrophilic Activation of Tryptophan Derivatives

A three-step mechanism involving the formation and rearrangement of an intermediate with indoline-azetidine spirocyclic core structure was shown by DFT computations to account for the electrophilic cyclization of tryptophan derivatives to hexahydropyrrolo[2,3-b]indoles. The corresponding 3a-bromo derivatives have been obtained in high yields and synthetically useful exo/endo ratios.