Some 25 years have elapsed since the topic of metalation reactions was reviewed by Gilman and Morton. The intervening years have been notable for intensive explorations in this area, in part because many organolithium reagents are now commercially available. Specifically, research efforts have been characterized by the discovery of new functional groups that promote metalation, elaboration of novel heterocyclic and olefinic substrates as metalatable species, recognition of new types of lithiating agents, and the continuation of efforts to define accurately the mechanism of metalation. Accordingly, heteroatom‐facilitated lithiation has become recognized as an increasingly important tool, not only in the elaboration of carbocyclic aromatic and heteroaromatic systems, but also in synthetic aliphatic chemistry. A few recent reviews have covered the topic in a more limited or less specific sense. It is the purpose of this chapter to survey and classify the vast accumulation of heteroatom‐facilitated lithiations recorded since the first coverage in Organic Reactions . As outlined by Gilman and Morton, the terms “metalation” in general and “lithiation” in particular denote any replacement of a hydrogen atom by metal or lithium. In this review, however, lithiation is defined as the exchange of a hydrogen atom attached to an sp 2 ‐hybridized carbon atom by lithium to form a covalent lithium‐carbon bond. More specifically, discussion is limited to those metalations that, through the influence of a heteroatom, are characterized by rate enhancement and regioselectivity. In fact, lithiation reactions of this type are noted for an extraordinarily high degree of regioselectivity, metalation generally occurring on the sp 2 ‐carbon atom closest to the heteroatom. Based on the relative position of the heteroatom, such lithiations are conveniently classified into two principal categories: alpha and beta ( ortho ) lithiations. In alpha lithiations the metalating agent deprotonates the sp 2 ‐carbon atom alpha to the heteroatom to form a carbonlithium bond. This sp 2 ‐carbon atom may be part of an olefinic or heteroaromatic π system. In beta lithiations the metalating agent is directed to deprotonate the sp 2 ‐carbon atom beta to the heteroatom‐containing substituent. The sp 2 ‐carbon atom can be part of an aromatic or an olefinic π system. It should be noted that the designation “ ortho metalation” is used specifically for the beta metalation of carbocyclic aromatic systems. This chapter surveys all systems in which alpha and beta lithiations have been observed, with the exception of ferrocenes.

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