Regioselectivity ortholithiation

To summarize, ortholithiation is a reaction with two steps (complex-formation and deprotonation) in which two features (rate and regioselectivity of lithiation) are controlled by two factors (coordination between organolithium and a heteroatom and acidity of the proton to be removed). In some cases, some of these points are less important (acidity, for example, or the coordination step). The best directing groups tend to have a mixture of the basic properties required for good coordination to lithium and the acidic properties required for rapid and efficient deprotonation. 

The ortholithiation of benzenesulphinamides 119 is of use in the regioselective synthesis of mefa-substituted compounds 120 the sulphinamide group is used to set up two ortho relationships and then removed reductively (Scheme 52) . The same concept has been explored with other sulphur-containing orf/zo-directors °. 

Numerous studies of the relative abilities of different ortholithiation directors to control regioselectivity have been published, and these are summarized in Section I.B. While Scheme 9 aims to place orf/zo-directors into an approximate order of potency, these studies show quite clearly that relative directing power depends on a variety of factors and varies from compound to compound. 

Epoxides will also capture organolithiums formed by deprotonation, notably cyclopropyllithiums and ortholithiated tertiary amides. Ortholithiated amides cyclise regioselectively in a valuable route to benzofurans such as 142 and 143 and (less efficiently) benzopyrans 144.70... 

Mechanisms and catalysis ch12 special about aromatic compounds Regioselectivity and ortholithiation ch24... 

In an early effort to introduce heteroatoms into [Injparacyclophane frameworks, the close relative 12.6 of the molecular square 12.1b with all methylene bridges replaced by dimethylsilyl functional groups was synthesized by Konig et using stepwise regioselective ortholithiation... 

Coordination of the chromium tricarbonyl group onto an arene enhances the kinetic acidity of the aryl C—bonds. In order to avoid nucleophilic attack of the organolithium reagent onto a CO ligand, the reaction has to be run at low temperature. The reaction is regioselective as ortholithiation is observed with arene substituted by OCH3, F, Cl. 

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