Aqueous Microdroplets Catalyze Groebke–Blackburn–Bienaymé Reactions

It has been proposed that water forms superacids/superbases and reactive oxygen species (hydroxyl radical, hydrogen peroxide, etc.) at the microdroplet interface. In comparison with the focus on the reactive oxygen species in an increasing number of efficient conversions without external redox agents, little attention has been paid to catalytic activities of the superacids/superbases. Herein, we elucidated the high catalytic activity of the superacids in microdroplets in a typical acidic Groebke-Bienaymé-Blackburn reaction (GBB, one of the most efficient strategies to afford imidazopyridine heterocycles). The GBB reactions at the micromolar scale can be catalyzed by the superacids in aqueous microdroplets at room temperature in good yields (82.5-93.0%), avoiding the use of external catalysts, high temperature, and long reaction time in classic strategies. When scaling up at the millimolar scale, the GBB reaction was still conducted at 32.2% yield with a scaled-up rate of 50.9 mg h-1 possibly due to the interfacial saturation, proving high catalytic efficiency of the superacids. Overall, this study proposed an efficient strategy for synthesizing imidazopyridine heterocyclic compounds.