Aryl and Heteroaryllithium Compounds by Metal - Halogen Exchange. Synthesis of Carbocyclic and Heterocyclic Systems

Abstract

The aromatic metalation - cyclization sequence is a valuable protocol for the regiospecific construction of carbocyclic and heterocyclic systems. Aromatic lithiation can be carried out by lithium - hydrogen or lithium - halogen exchange. The latter procedure, though mechanistically controversial, is the method of choice to introduce specifically a lithium atom into a given, non-activated position of the aromatic ring. Once generated, the aryllithiums may react with external or internal electrophiles and thus give rise to cyclization reactions, which are known as Parham cyclization. In addition to the carbon - carbon bond formation, the aromatic lithiation allows the introduction of further functionality to the molecule. Therefore, strategies based aromatic lithiation can play a crucial role in natural products synthesis. In this review we will survey some recent advances on the application of the aromatic lithiation - cyclization sequence for the synthesis of different types of carbocycles and heterocycles. We have limited it to the metalation reactions, where the aryl and hetero-aryllithium intermediates are generated by the metal - halogen exchange reaction. Major emphasis will be placed on stereoselectivity of the metalation - cyclization sequence, since it has received only sporadic attention.