Friedel-Crafts As a New Approach To Construct Potential Bioactive Scaffolds Using Indolizines And Isatins.

Friedel-Crafts alkylation (FC-alk) is one of the oldest and well known reactions in organic chemistry and still is object of study. Currently, this reaction can be carried out by applying a wide range of conditions, such as Lewis or Brønsted acid catalysts, as well as employing heteroarenes as nucleophile of the reaction.1 Despite of that, indolizines are still poorly explored for this transformation.2
Continuing our investigations on functionalization/derivatization of indolizines,3 we disclose herein an unprecedented phosphoric acid catalyzed addition of indolizines to isatins. Water is the best solvent for this transformation, which could be dramatically accelerated by the use of a surfactant (SDS). Employing this methodology, new indolizine FC-alk adducts were accessed in good to excellent yields.
Indolizines4 and isatin5 are found as the core of bioactive molecules, thus the adduct engendered by the FC-alk using these two molecules can furnish a new kind of bioactive scaffold.