Hydrogen—lithium exchange

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. 

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 - . 

The lithio derivatives 63 are converted into deuteriopyrazines 64, and their yields can be equivalent to those of the hydrogen/lithium exchange (Scheme 15). As a result, the lithiation of chloropyrazines and pyrazinethiocarboxamide is optimized at —70 to —75°C, whereas that of methoxy- or acylamino-pyrazines at 0°C. Conversely,... 

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... 

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

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). 

Hydrogen-lithium exchange with lithium or lithium-bases... 

First, in a hydrogen-lithium exchange of the 1-H, methoxyallene is converted into a C-nucleophile, which attacks the keto-ftinctionality of 20 to form the tertiary alcohol 22 in 75 % yield. As the r -face of the ketone is blocked by the isopropylidene bridge of the six-membered ring, the nucleophilic attack can only occur from the 5 z-face. 

The introduction of an additional stabilizing influence on the a-alkoxy anion may serve two purposes. Firstly the anions are easier to prepare, generally by hydrogen-lithium exchange. Secondly the effective oxidation state of the a-carbon atom is increased. 

Reductive coupling of a 3- or a 1-halocyclopropene to form a 3,3 - or 1,1 -bicyclopropenyl, respectively, may be brought about either photolytically or via an organometallic intermediate. The latter can also be generated by hydrogen-lithium exchange and transmetalation. Examples are the formation of 1, 2, and... 

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...

A silylation step is interposed between the first, second, and third hydrogen-lithium exchange in other words, the threefold electrophilic substitution is mediated by monometalated intermediates [128]. 

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

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