Directed Metalation of Arenes with Organolithiums, Lithium Amides, and Superbases

The metalation of arenes in the vicinity of an appropriate directing metalation group (DMG) by organolithiums, lithium amides, and superbases is one of the most powerful method for the regioselective preparation of synthetically useful polyfunctional arenes. This chapter aims to provide a broad understanding of the theory and practices of aromatic metalation reactions, which allow direct functionalization of unactivated aromatic C—H bonds by the stoichiometric formation of aryllithium(potassium) intermediates, namely, (i) directed ortho metalation (DoM) of arenes bearing one or more DMGs, (ii) directed remote metalation (DreM) of polyarenes, (iii) peri metalation of naphthalenes, and (iv) metalation of metal-complexed arenes (mainly chromium complexes). The main analytical methods and techniques (crystallography, NMR spectroscopy, quantitative analysis) and important synthetic applications are presented to highlight the recent advances of these techniques and their impact for improving the design of pharmaceutical compounds and organic materials.