Development of the synthetic method for an optically active quarternary carbon by the use of organocatalysis and its application for the synthesis of biologically active compounds

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Thiazloes are among the most important heteroaromatics with pharmaceutical importance and as starting material of thiazolium salts, which attract the attention for the utility as organocatalysts. Direct coupling of thiazoles with aromatic halides or triflates is preferable method for preparation of derivatized thiazoles in terms of its synthetic simplicity. In the course of the synthetic study on chiral thiazolium salts, we encountered direct palladium-catalyzed cross-coupling reaction of 2-trimethylsilylthiazoles with biaryl triflates leading to 2-arylthiazoles. 2-Trimethylsilylthiazoles serve as an efficient counterpart for direct palladium-catalyzed cross coupling reaction with aromatic triflates without any fluoride anion source to afford 2-arylthiazoles.Thiazolium salts drived from 5-(2-hydroxyethyl)-4-methylthiazole with benzyl chloride have generally been used as the catalyst for the Stetter reaction. We have succeeded in preparing the reusable thiazolium salts from 5-(2-hydroxyethyl)-4-methylthiazole with fluorous chemistry. The fluorous tags were introduced into the hydroxyl group of that thiazole and the nitrogen atom of thiazole ring by its quarternisation with fluorous benzylhalide analogue. The synthetic utility of the fluorous thiazolium salts was similar to that of the standard catalyst. In the intramolecular Stetter reaction, the desired product was produced in 82% yield by the use of the fluorous catalyst. Also, the fluorous catalyst survived 5 cycles in the intromolecular Stetter reaction.