Pd-Catalyzed Cross-Coupling Strategies in Thiazole Chemistry

Within this contribution the synthesis of anilino-substituted bithiazoles as potentially bioactive compounds is reported. The key chemical transformations in the applied synthetic strategy were Pd-catalyzed cross coupling reactions which were used for the formation of various bithiazoles. Different cross coupling methodologies were investigated. Starting from 2-thiazolamine the desired metal organyls were prepared in two steps. Besides the well documented Stille and Negishi reaction on thiazole derivatives, a new method could be established. After successful preparation of the first thiazoleboronic acid ester, Suzuki-Miyaura reactions were performed. Upon reaction with various bromo-thiazoles the desired bithiazole derivatives were obtained, whereby the Stille reaction gave the best results compared to the other two methods. Subsequently the chloro atom was used for a nucleophilic exchange reaction with aniline derivatives to give the target compounds.