Enantioselective Merger of Aminocatalysis with [pi]-Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo- and Heterocycles

The metallo-organocatalyzed enantioselective synthesis of various five-membered carbo- and heterocyclic structures through the merger of aminocatalysis with the catalytic indium(III) or copper(I) activation of [alpha]-disubstituted formyl alkynes is described. The use of indium trichloride associated with the (R)-1,1'-bis-(2-naphthylamine) ligand led to encouraging results with up to 85:15 enantiomeric ratio. After a careful examination of several other strategies, the best synergic catalytic system, which combines a chiral copper(I) complex with cyclohexylamine, afforded the enantioselective preparations of cyclopentane, indane, and pyrrolidine scaffolds with moderate to excellent control of the all-carbon quaternary stereogenic centers created through such cyclization processes. [PUBLICATION ABSTRACT]