Directed Remote Aromatic Metalations: Mechanisms and Driving Forces

Directed remote aromatic metalations are useful synthetic transformations allowing for rapid regioselective access to elaborate highly substituted carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle of data reported on directed remote aromatic metalations. Through a careful analysis of critically selected examples, advanced rationalizations of remote metalation regioselectivities are presented. These extend beyond the complex-induced proximity effect (CIPE). Mechanisms, driving forces, and parameters influencing remote metalations are discussed. An understanding of these metalation mechanisms enables more accurate predictability of justification of regiochemical outcomes of these useful synthetic transformations.