Clay/Water mixtures - A heterogeneous and ecologically efficient catalyst for the three-component stereoselective synthesis of tetrahydroquinolines

The three-component synthesis of tetrahydroquinolines 5 from aromatic amines i, aromatic aldehydes 2 and cyclopentadiene (4) can be efficiently performed in water in the presence of the commercially available bentonite Bieliaca. The overall process involves the rapid initial production of the imines 3, which subsequently undergo aza-cycloaddition processes with cyclopentadiene, affording products in good yields and with excellent selectivities. The cycloaddition step is regiospecific and stereospecific, exclusively giving the endo product. It was possible to reuse the catalyst several times without lowering its efficiency. The process represents a clean, safe and environmentally friendly route for the production of a class of natural products displaying a wide range of biological activities.