Development of an electrophilic amination methodology for aromatic indolizines

Abstract

Indolizines are heteroaromatic molecules that have a six-membered ring fused with a five-membered ring, with a nitrogen atom in the center, they are also called pyrrolo[1,2-a]pyridine. Due to their electronic and fluorescent characteristics, they have also been used for photoresponsive materials and dyes. Amino groups are very interesting substituents for different scaffols, as they can act as building blocks and generate more complex molecules or with greater pharmacological potential. There are several methodologies for insertion of amino groups (amination) in different systems, some of them being: the reduction of nitro-compounds, the direct functionalization of the C-H bond in aromatic rings, nucleophilic amination of deactivated systems and even electrophilic amination. Electrophilic amination reactions involve an electrophilic nitrogen source and a nucleophilic carbon, and reagents derived from hydroxylamines and oxaziridines may be used. Although there are several methodologies for the amination of different heterocycles, there is no consolidated methodology for the amination of indolizines, therefore, this project aims to develop a methodology for the electrophilic amination of indolizines, based on a strategy that employs the reaction of reagents organometallics with electrophilic oxaziridines. This approach should lead to the preparation of different aminated indolizines with novel structures in the literature, which can be used as a building blocks for other more complex structures with varied and fused heterocycles.