Halogenated 2'-chlorobithiazoles via Pd-catalyzed cross-coupling reactions.

Halogenated bithiazoles allow facile further functionalization and are, therefore, suitable intermediates for the synthesis of compounds with interesting biological activity or material science properties. The applicability of three coupling methods (Negishi, Suzuki, and Stille) for the synthesis of the title compounds was compared. The Negishi method proved to be troublesome, and side reactions were predominant. The synthesis of the first thiazoleboronic acid ester offered a new method for the formation of bithiazoles, not generally applicable so far. The lower toxicity compared to that of tin organyls make this method an approach with interesting perspectives. The Stille coupling proved to be superior to the other methods and enabled the synthesis of the title compounds with diverse connectivity.