One-Pot Tandem Protocol for the Synthesis of 1,3-Bis(β-aminoacrylate)-Substituted 2-Mercaptoimidazole Scaffolds

We have developed a palladium-catalyzed cross-coupling reaction of isocyanides with alpha-diazoacetates to form active ketenimines and following a 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed aza-Mannich type reaction with various 2-mercaptoimidazoles for the synthesis of 1,3-bis(beta-aminoacrylate)-substituted 2-mercaptoimidazole derivatives with structural diversity. In addition, the use of 1H-benzo[d]imidazol-2-ol as the reaction partner also allowed the formation of 1,3-bis(beta-aminoacrylate)-substituted 2-benzimidazolinone derivatives with moderate yields (34-52%). In the aza-Mannich reaction, the regioselectiveN-attack rather than S-attack or O-attack at the electrophilic central carbon of ketenimines was observed. This tandem sequence is efficient since two C=C and two C-N bonds are consecutively created in one-pot.