A Boronic Acid Catalyzed Route to Imidazoles. Synthesis of LFA-1 Antagonists

Significance

Reported is the synthesis of 1H-­imidazo[1,2-a]imidazole-2-ones 2 via the boronic acid catalyzed cyclodehydration of 1 in the presence of trimethylorthoformate. Investigation of this procedure demonstrated the necessity of the acetal functionality present in 1 for effective product formation. Furthermore, bulkier acetals (such as diethyl acetal) proved less efficacious in the transformation. Control reactions conducted demonstrated that the cyclic urea 4 is not an intermediate in the reaction as it fails to progress to the desired product under the optimized conditions. In addition, the reaction is reported to be highly scalable (>1 kg), although only limited substrate scope was examined.