Strategies Based on Aryllithium and N-Acyliminium Ion Cyclizations for the Stereocontrolled Synthesis of Alkaloids and Related Systems

The intramolecular alpha-amidoalkylation reactions of aromatic and heteroaromatic ring systems constitute a versatile approach for the synthesis of nitrogen heterocyles in a diastereoselective or enantioselective fashion. On the other hand, the intramolecular reactions of aryllithium compounds have also been extensively used in the synthesis of carbocycles and heterocycles. The use of imides as internal electrophiles is particularly attractive because of the potential to introduce diverse functionality into the cyclized products by subjecting the resulting alpha-hydroxylactams to intermolecular reactions with nucleophiles through intermediate N-acyliminium cations. This metalation/cyclization/alpha-amidoalkylation sequence can be diastereocomplementary with intramolecular alpha-amidoalkylation reactions via N-acyliminium ions derived from the corresponding imides. This review focuses on recent developments of synthetic methods for heterocyclic systems (alkaloids and related systems) based on aryllithium compouns and N-acyliminium ion cyclizations, with special attention to the stereocontrolled formation of carbon-carbon bonds.