Lithium elimination

The first stable silaallene, 56, was synthesized in 1993 " " by the intramolecular attack of an organolithium reagent at the /f-carbon of a fluoroalkynylsilane (Scheme 16). Addition of two equivalents of r-butyllithium in toluene at O C to compound 54 gave intermediate 55. The a-lithiofluorosilane then eliminated lithium fluoride at room temperature to form the 1-silaallene 56, which was so sterically hindered that it did not react with ethanol even at reflux temperatures. 1-Silaallene 56 was the first, and so far the only, multiply bonded silicon species to be unreactive toward air and water. The X-ray crystal structure and NMR spectra of 56 is discussed in Sect. IVA. 

The organolithium compound which gives rise to the compound (11) can itself eliminate lithium fluoride, and mass spectrometric and other evidence has shown that this reaction is repeated until all the possible eliminations and subsequent additions have taken place 27h... 

An alternative approach was used in the synthesis of the herbicide 530, where the sulfoxide 529 was converted to 530 in a single step by heating with lithium chloride in refluxing pyridine <1997TL4339>. The one-pot transformation involves sigmatropic sulfoxide elimination, lithium chloride-induced demethylation of the carbomethoxy group, decarboxylation, and a final isomerization/aromatization step <1997TL4339>. 

Bromo-l-lithiocyclopropanes, readily obtained by transmetalation of 1,1-dibromocyclo-propanes with butyllithium in tetrahydrofuran at — 100 CC, undergo addition to aldehydes and ketones forming bromohydrins. On warming, before workup, the adducts from ketones (but not from aldehydes) eliminate lithium bromide and cyclizc to oxaspiropentanes, which may be rearranged to cyclobutanones by treatment with acids (Table 6).76-78... 

Evidence for such reactions in methylmethacrylate polymerizations was obtained by termination of polymerizations with acetic acid followed by measurements of methanol formed (119, 120). Fig. 6 shows typical results obtained. It is assumed that the methanol found corresponds to lithium methoxide in the reaction mixture. Some methanol might in fact be produced only in the termination reaction from pseudo-cyclized species (cf. p. 82). In addition the tertiary alkoxides formed by attack of the initiator or growing polymer chains on the carbonyl group of the monomer might not eliminate lithium methoxide immediately but would do so on termination with acetic acid. In any case much of the methanol formed corresponds to actual alkoxide in the reaction mixture and the results give a minimum value of the concentration of species inactive in polymerization. For brevity it will be referred to as lithium methoxide. 

Perfluoroalkyllithium compounds can eliminate lithium fluoride to afford fluoroalkenes, e.g. 12 and 13.151-214... 

Conjugated alkenes which are part of aromatic rings are occasionally carbolithiated, but unless they are stabilised by further conjugation the products are unstable. For example, organolithiums will add to naphthalene, but the product eliminates lithium hydride to give the... 

Carbolithiation of a trifluoromethyl-substituted alkene 59 produces an unstable intermediate 60 which eliminates lithium fluoride to give gem-difluoroalkenes 61.35... 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

Only the kidneys eliminate lithium. Like sodium, it is filtered by the glomerulus and 80% is reabsorbed by the proximal tubule but it is not reabsorbed by the distal tubule. Intake of sodium and water are the principal determinants of its elimination. In sodium deficiency lithium is retained in the body, thus concomitant use of a diuretic can reduce lithium clearance by as much as 50% and precipitate toxicity. Sodium chloride and water are used to treat lithium toxicity. 

When starting from ( )-l-o-bromophenyl-2-trimethylsilylethene 31 [30] the postulated trilithium compound 26 is obtained by addition of lithium metal to 32 in this case diethoxymethane (DEM) [31] is the most suitable solvent. Compound 26, however, eliminates lithium hydride very easily, so only a small amount (7 %) of the trimethyl derivatives (erythro and threo 33, 1 4) is obtained. As the main product 28 (66 % yield) is again observed, additionally 9 % of ( )-l-o-tolyl-2-trimethylsilylethene originating from 32 is found (Scheme 7). 

Finally the intermediate 25 is synthesized by adding lithium metal to E)- A, R = Ph, in the more polar solvent THF, here not only the [l,4]-proton shift is supressed, neither does 14 eliminate lithium hydride under the reaction conditions, probably a solvent separated ion pair has to be anticipated for the lithium in the benzylic position of 25 as the cause for this stability. 

Alkynyltrimethylsilanes. Arylethynylsilanes are obtained from aromatic nitriles by reaction with tris(trimethylsilyl)methyllithium which is in turn derived from the silane (MeLi/THF, 65°). The initial adducts eliminate lithium hexamethyldisilazide on thermolysis in benzene. 

Monomeric 1,2-dilithioethane 1 should thus be marginally unstable thermodynamically toward dissociation into ethylene and Li2, but stable toward the loss of lithium hydride or of hydrogen. Equation 2, however, is not in agreement with experimental results of Rautenstrauch and Bogdanovic who found that 1,2-dilithioethane 7 — if it is formed at all by the addition of lithium to ethylene — looses lithium hydride spontaneously. These findings prompted a reconsideration of the nature of 1,2-dilithioethane 7 and its tendency to eliminate lithium hydride >. Most interestingly it was found that the vinyllithium-lithium hydride complex 10 is... 

The dilithium salt of the corresponding dimethylpropargylic alcohol 148 interestingly adds ethyllithium in a different manner. The primarily formed 2,3-dilithio-2-pen-tenolate 149 obviously eliminates lithium hydride which attacks the allene intermediate 150 splitting off lithium oxide in an Sj 2 reaction. The endproduct, an EIZ-mixture of 3-lithio-2-methyl-2,4-hexadiene 757 finally was obtained in 30% yield The last step was independently shown to take place by treating the corresponding allenic alcoholate with lithium hydride... 

The lactone 168 is lithiated at the benzylic site by lithium tetramethyl piperidide (LiTMP) 167 to give 172. Notice that this charge can delocalise into the carbonyl group and that ortho-lithiation between the two methoxy groups does not occur. One of the reactive species then is 172. The aromatic bromide 171 is lithiated ortho to the bromide 174, eliminates lithium bromide, and generates a benzyne 173. These two species then combine. 

These investigations of lithium handling by the kidneys have provided information which is useful for prevention and treatment of lithium intoxication. In general, all conditions associated with salt depletion strongly impair renal capacity to eliminate lithium. 

It is advisable to carry out derivatization reactions as soon as possible particularly in THF too much delay may give rise to reduced yields owing to reaction of butyl bromide with aryllithium. In most cases this alkylation causes an observable heat effect when the temperature is allowed to reach —10 °C in the case of 0-LiC6H4OCH3, however, this reaction is markedly slower. 0-LiC6H4F eliminates lithium fluoride at temperatures above —40 °C [221]. 

By use of the dithane (20) [e./., compound (4)], prepared from 4,6-dideoxy-D-xylo-hexose by thioacetalation and base-catalysed elimination, lithium... 

While no concerted attempts to prepare selenaarynes have been reported, the chemistry of several potential precursors has been examined. The 2-lithio-3-bromo derivatives 490 and 491 react with electrophiles as expected for aryllithium reagents and show no tendency at —70°C to eliminate lithium bromide to form a 2,3-didehydroselenophene (492). Similar observations have been reported for the benzolog 493 and the possible aryne 2,3-didehydrobenzo[ft]selenophene 494. As in the corresponding sulfur and oxygen heterocycles, this unusual stability of the 2-lithio derivatives is probably related to the ability of the heteroatom to stabilize an adjacent carbanion. ... 

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