Multicomponent double Povarov reaction for julolidine: Synthesis and mechanistic insights

Abstract

Julolidines constitute a class of N-heterocyclic molecules that behave as molecular rotors. Due to their fluorescent properties, they are applied in a wide range of technological fields, such as the production of solar cells, fluorescent biomarkers or bioimaging, and photoconductive materials. In the present work, we developed a methodology for the synthesis of julolidines through the one-pot tandem reaction-based application of multicomponent double Povarov reaction (MCPR) using BF3.OEt2 as the catalyst (25 mol%), star anise oil rich in trans-anethole as the substrate, and water as the solvent in reactions at room temperature. The julolidines were obtained with total yields ranging from 55 to 95 %. A mechanistic study allowed for the conclusion that these MCPRs take place through an ionic mechanism and also that released protons by the reaction between BF3.Et2O and water are involved in the catalytic process. After extracting the products from the reaction medium, the remaining aqueous phase containing the catalyst can be reused for up to six catalytic cycles with a minimal loss of catalytic efficiency. DFT calculations were conducted to investigate the catalytic cycle using BF3.Et2O and ZnCl2 as catalysts. The results indicate that the formation of iminium ions is a prerequisite for the progress of the reaction (MCPR). When BF3.Et2O and water are involved, the reaction proceeds via Brønsted catalysis, and the formation of iminium ions occurs in an exothermic and spontaneous process. However, when the ZnCl2 is used, the process is Lewis catalyzed to form the first iminium ion and is endergonic, shifting the equilibrium towards the reactants and inhibiting the cyclization.