Reference EntryDOI
Heteroatom‐Facilitated Lithiations
TLDR
A comprehensive survey of heteroatom-facilitated metalation reactions can be found in this article, where the authors classify them into two categories: alpha and beta (ortho) lithiations.Abstract:
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 sp2-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 sp2-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 sp2-carbon atom alpha to the heteroatom to form a carbonlithium bond. This sp2-carbon atom may be part of an olefinic or heteroaromatic π system.
In beta lithiations the metalating agent is directed to deprotonate the sp2-carbon atom beta to the heteroatom-containing substituent. The sp2-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.
Keywords:
lithiations;
alpha lithiations;
beta lithiations;
scope;
limitations;
alpha activating atom;
oxygen;
sulfur;
nitrogen;
selenium;
tellurium;
halogens;
beta-directing atom;
substrates;
enamines;
vinyl isocyanides;
formamides;
pyrroles;
indoles;
pyrazoles;
imidazoles;
triazoles;
tetrazoles;
alkyl vinyl ethers;
pyrazoles;
pyridines;
pyrimidines;
furans;
oxazolines;
oxazoles;
sulfides;
sulfoxides;
thiophenes;
electron-withdrawing groups;
vinyl halogens;
amines;
ethers;
sulfones;
amides;
alcohols;
ketones;
experimental proceduresread more
Citations
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Book ChapterDOI
X-ray structural analyses of organolithium compounds
TL;DR: In this article, the X-ray structural analyses of organolithium compounds have been discussed, and a number of mixed-metal organometallic compounds with a single contact between lithium and a carbon atom have been characterized.
Journal ArticleDOI
C–H Functionalization of Azines
TL;DR: This review describes recent advances in the C-H functionalization of azines categorized as follows: SNAr reactions, radical reactions, deprotonation/functionalization, and (4) metal-catalyzed reactions.
Journal ArticleDOI
The Structure of Lithium Compounds of Sulfones, Sulfoximides, Sulfoxides, Thioethers and 1,3-Dithianes, Nitriles, Nitro Compounds and Hydrazones
TL;DR: In this article, the authors summarize recent research into the structures of the acceptor-substituted lithio compounds of sulfones, sulfoximides, sulfoxide, thioethers and 1,3-dithianes, nitriles, nitro compounds, and hydrazones.
References
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Journal ArticleDOI
Preparation, metallation and alkylation of allenyl ethers
TL;DR: Propargyl ethers HCCCH2OR [R = alkyl or-CH(CH8)(OC2H5)] have been isomerized with good yields into the corresponding allenyl ether's CH2CCHOR by warming with potassium tert-butoxide at 70°.
Journal ArticleDOI
Aromatic Nucleophilic Substitution Reactions.
Journal ArticleDOI
Colored indicators for simple direct titration of magnesium and lithium reagents
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