CeCl3·7H2O/NaI as Lewis acid catalyst in the Povarov reaction for the synthesis of functionalized tetrahydroquinolines

Many different biologically active compounds contain the widespread scaffold of tetrahydroquinolines. Hence the interest toward their synthesis has stimulated the development of several synthetic strategies, among which the Povarov reaction is one of the most applied. The performance of this three-components imino Diels-Alder reaction can be improved by Lewis acid catalysis. In the last years the search for more economic and environmentally benign synthetic methodologies has stimulated the use of nontoxic and nonexpensive catalytic systems, and in this perspective Cerium trichloride has became interesting because of its low toxicity and cost and for the ease of application also in non anhydrous conditions.2,3 Here we describe the study of the CeCl3·7H2O/NaI system as Lewis acid catalyst in the Povarov reaction for the synthesis of substituted tetrahydroquinolines. The reaction proceeds well, in acceptable reaction times and up to 86% yield. Both syn and anti diastereomers of the final tetrahydroquinoline can be obtained preferentially, depending on the reaction conditions, because the stereoselectivity is opposite in acetonitrile or in solventless conditions. Also substituted anilines and aromatic aldehydes have been employed with good results. A further investigation was made about the mechanism, to understand the formation of the main byproducts.