Hydrogen-lithium exchange reactions

Hydrogen-lithium exchange reaction was first utilized to prepare the stable perfluorobicyclo[2,2,2]oct-l-yl lithium reagent [8] (Scheme 2). 

Scheme 5.12 Preparation of organolithium compounds (a) halogen-lithium exchange reaction (b) hydrogen-lithium exchange reaction...

Scheme 10.5 Hydrogen-lithium exchange reaction of phenyl isonicotinamide and subsequent reaction with a ketone to synthesize spiro lactone...

The application of hydrogen-lithium exchange reactions is limited due to possible reactions of nucleophilic organolithium reagents or aryUithium intermediates with... 

Kohn and Taylor (40) also studied the influence of illumination on the hydrogen-deuterium exchange reaction using specimens of barium, calcium, lithium, and sodium hydrides. If the specimens were annealed in the hydrogen atmosphere, the photocatalytic effect on these specimens was positive. And if the specimens of the same hydrides were preliminarily calcined in vacuum, the irradiation of these specimens retarded the reaction. 

In principle, each of the above protodelithiation reactions is in equilibrium. It is clear that, in practice, they are not. The protonating species, HBr, isopropanol and 2-butanol, are simply too acidic for the reaction to be reversible. Although the hydrogen/lithium exchange equilibria cannot be smdied in both directions, halogen/Uthium exchange reactions with aryl substituents evidently are true equilibrium processes. Winkler and Winkler studied reaction 11 (among others), in either diethyl ether or in THF at 25 °C. 

This procedure was extended to a method for asymmetric synthesis of optically active epoxides starting from optically active sulfoxides. As the oxiranyUithium 131 reacts with the acidic hydrogen of the n-butyl aryl sulfoxide, the introduction of electrophiles to the reaction mixture was problematic. Therefore, the reaction was performed by addition of 1 equivalent of f-C4H9Li at — 100°C to 130 and the sulfoxide-lithium exchange reaction was found to be extremely rapid (within a few seconds at this temperature). Moreover, as f-butyl aryl sulfoxide 138 has now no more acidic hydrogen, the addition of several electrophiles leads to functionalized epoxides 139 (equation 48). ... 

Whereas carbenoid character is definitely present in metalated alkyl vinyl ethers, lithiated alkyl and aryl vinyl sulfides and thioesters, which are easily available by hydrogen-lithium exchange, do not display carbenoid-typical reactions . They rather behave like nucleophilic reagents, so that their discussion is beyond the scope of this overview despite their utility in synthesis The same appiies to various derivatives of enamines, deprotonated in the vinyiic a-nitrogen position - . 

Base-induced cleavage of 1,2,3-thiadiazoles is a useful method of generating the anions 79. Raap and Micetich first reported the reaction with 4-phenyl-1,2,3-thiadiazole (80) (R = Ph). This compound undergoes hydrogen-lithium exchange at C-5 with butyllithium. The lithio derivative is unstable above — 65°C and the anion (79) (R = Ph) can be intercepted in good... 

Scheme 15. Hydrogen-lithium exchange followed by electrophilic substitution. Reaction conditions (i) w-BuLi, rt, electrophile...

As Scheme 59 illustrates, the reaction involves the hydrogen-lithium exchange of phenyl isonicotinamide 202, in the presence of H-BuLi 74/LiBr 203, followed by a reaction with ethyl-4-oxocyclohexanecarboxylate 204 to afford the target spiro lactone 201 as a mixture of cis/trans isomers. In the presence of any residual dilithiated intermediate 205, the spiro lactone 201 can undergo a second reaction to afford the by-product 206. Conducting the reaction in a microflow reactor, comprising of static mixers and... 

The insertion of elemental tellurium into C — Li or C — Na bonds is a convenient method for the preparation of alkali metal tellurolates. Many organic lithium compounds are commercially available or can be prepared, for instance, by halogen-lithium or hydrogen-lithium exchange. The reactions of the organic lithium compounds with elemental tellurium are performed in inert organic solvents such as diethyl other, tetrahydrofuran, tetrahydrofuran/hexane, or diethyl ether/benzene at temperatures (— 196° to + 20°) compatible with the stability of the organic lithium compound. The applicability of this reaction for the synthesis of aliphatic, aromatic, and heteroaromatic lithium tellurolates is documented in Table 1 (p. 155). 

The simplest reaction characteristic of compounds that are regarded as salts of carbanions is that of proton transfer (see Proton Transfers Involving Anions and Dianions) and a number of these have been studied. A typical example is the reaction of methane with lithium amide. This reaction is a model for many known hydrogen isotope exchange reactions of hydrocarbons with lithium and cesium cyclohexylamide whose kinetics have been measured in cyclohexylamine. The model reaction does involve a preliminary weakly bound complex that isomerizes via a transition structure to methyllithium coordinated to ammonia (Figure 3). 

The w-cyclopentadienyl rings of ferrocene are readily metalated for example by treatment with butyl-lithium. This metalation is similar to the hydrogen/metal exchange reactions typical of, for example, certain benzenoid hydrocarbons, (p 48). Mixtures of mono- and di-metalated products are frequently obtained. A suitable method of preparing 1,1 -dilithioferrocene is given on p 49. 

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