A Cascade Reaction To The Synthesis Of Trifluoromethyl Substituted Pyrroles

The incorporation of trifluoromethyl group often leads to significant enhancement of thephysical and chemical properties of molecules such as solubility, metabolic stability, andbioavailability, etc., and thus trifluoromethyl-substituted pyrrole have so far been widelyapplied in the fields of pharmaceutical, agrochemicals, functional materials due to theirspecial properties.Compound N-tosylated imine esters with trifluoroacetic anhydride (TFAA) in the presenceof Phosphine catalyst were chosen to afford the corresponding2-trifluoromethylated pyrrole.And further,2-trifluoromethyl-3-trifluoroacetyl substituted pyrrole derivatives are constructedbasing on the method proposed.Two main conclusion can be drawn as listed below:1. A novel and effective method for synthesis of trifluoromethylated pyrrole is proposedin this thesis. A series of optimization of the reaction condition is carried out, includingcatalysts, solvents and other factors. Further optimizing conditions reveals that the best resultof the99%yield was achieved using1.0equiv of PPh3and1.5equiv of TFAA. Then thescope of the reaction is investigated using various substrates, including neutral,electron-withdrawing and-donating groups and heterocyclic substituted unsaturated imineesters. Results show that all substrates can participate in this cascade reaction well with goodyields.2. The synthesis and characterization of2-trifluoromethyl-3-trifluoroacetyl substitutedpyrrole are then discussed, including the characterization of five different pyrrole derivatives.As is revealed, the proposed reaction is operationally simple, fast, with high yield,amenable to scale up. This method is expected to show potential application to the synthesisof trifluoromethyl-substituted pyrrole.