General and Efficient Organocatalytic Synthesis of Indoloquinolizidines, Pyridoquinazolines and Quinazolinones through a One-Pot Domino Michael Addition-Cyclization-Pictet-Spengler or 1,2-Amine Addition Reaction

An asymmetric organocatalyzed reaction sequence involving a Michael addition of various 1,3-dicarbonyl compounds to alpha,beta-unsaturated aldehydes with subsequent diastereoselective Pictet-Spengler cyclization has been developed. The substrate scope was found to be general and optically active indoloquinolizidines were isolated as single diastereomers in high yields with high to excellent enantioselectivites. In addition to tryptamine, the reaction has also been successfully applied to other nucleophiles including o-aminobenzylamine and anthranilamide giving rise to pyridoquinauolines and quinazolinones.