A Comparative Study on the Groebke-Blackburn-Bienaymé Three-Component Reaction Catalyzed by Rare Earth Triflates under Microwave Heating

Abstract

Over the last twenty years, the Groebke-Blackburn-Bienaymé (GBB) reaction has been emerged as a powerful tool to access different nitrogen-based heterocycles as privileged scaffolds in medicinal chemistry. This multicomponent reaction is usually catalyzed by ordinary Brønsted or Lewis acid catalysts. Herein, we present a comparative study on the catalytic efficiencies of different rare earth triflates in GBB reactions under microwave heating, involving 2-aminopyridine or 2-aminothiazole, as aminoazole component, and different aldehydes and aliphatic isocyanides. The use of gadolinium(III) triflate as cheaper alternative catalyst for the most commonly used scandium(III) triflate was acknowledged for the first time, and a library of twenty three imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles could be obtained in good to excellent yields.

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the reactivity of the imine formation [ 24 ]. The most common catalysts are those derived from triflate salts such as Sc(OTf) 3 [ 25 ], Yb(OTf) 3 [ 26 ], In(OTf) 3 [ 27 ] and Gd(OTf) 3 [ 28 ], and inorganic Brønsted or Lewis acids like HClO 4 [ 29 ], ZrCl 4 [ 30 ], InCl 3 [ 31 ], BiCl 3 [ 32 ], RuCl 3 [ 33 ], NH 4 Cl [ 34 ], HCl [ 35 ], LaCl 3 ·7H 2 O [ 36 ], and ZnCl 2 [ 37 ], or organic acids such as p -toluenesulfonic acid (PTSA) [ 38 ], TFA [ 39 ], and AcOH [ 40 ], etc. Nonetheless, most of these acids have major drawbacks such as being expensive, dangerous, strong oxidizing, or even potentially explosive, with long reaction times being required.…”