General Chiral Catalysis: A Cinchona Thiourea–Pyridoxazoline Scaffold as Both Organocatalyst and Chiral Ligand for an Enantioselective Mannich Reaction between α-Aminomaleimides and Benzothiazolimines

Abstract

For proof of a new concept of general chiral catalysis, a series of new bifunctional chiral catalysts integrated with both cinchona alkaloid thiourea and pyridine-oxazoline scaffolds were devised and prepared. Using as independent organocatalysts, a new Mannich reaction between α-aminomaleimides and benzothiazolimines with acceptable enantioselectivities (up to 75% ee) has been disclosed. Served as a chiral ligand, the new organocatalyst synergically works with Cu(OTf)₂ to catalyze the reaction in excellent enantioselectivities (up to 96% ee) with good yields under mild conditions even in a scale-up preparation. Both the substrates and the final multifunctional chiral adducts may provide a possibility for the development of new pharmaceutical entities and chiral ligands.