Cerium derivatives as catalysts in the reaction of nitrones with indoles

Nitrones are involved in numerous reactions with nucleophiles and among the other also electron rich aromatic compounds can be made to react with them. In particular indole derivatives are of particular interest, owing to the widespread presence of indole scaffolds among biologically active compounds and natural substances. No reaction occurs when a nitrone and indole are mixed together in polar or apolar solvents as toluene, methanol or dichloromethane, then activation of nitrone is necessary to achieve the raction. The common activation of nitrones by protonation of the oxygen atom collides to the known tendency of indoles to polymerize in the presence of protic acids. In this sense the aim of this work is to explore the possibility to use Cerium derivatives as catalysts for the reactions of nitrones with indole. Efficient electrophilic substitution reaction of indoles with various carbonyl compounds, proceeds easily in solvent free conditions using CeCl3.7H2O-NaI-SiO2 system promoter to afford bis indolyl alkanes in high yields.1 Furthermore, the same promoting system was used in the Michael addition of cyclic enones to indole with good results. Preliminary data show that the reaction between pyrrolidine nitrone and indole takes place with CeCl3.7H2O-NaI-SiO2 promoting system, as showed in Scheme 1. Further studies are in progress to set the best composition of the promoting system. At the same time Cerium triflate and other Cerium derivatives are experimented, as Lewis acid catalysts for this reaction. This results allow the application of the reaction towards chiral pyrrolidines, to develop the stereoselective synthesis of chiral derivatives with biological activity.