Bases Methyllithium

A vinylogous Shapiro reaction was used in a four-step synthesis of bicyclic diene (7) from n-pincne (4). In place of the usual base (methyllithium), 4 equiv. 

Anionic polymerization of vinyl monomers can be effected with a variety of organometaUic compounds alkyllithium compounds are the most useful class (1,33—35). A variety of simple alkyllithium compounds are available commercially. Most simple alkyllithium compounds are soluble in hydrocarbon solvents such as hexane and cyclohexane and they can be prepared by reaction of the corresponding alkyl chlorides with lithium metal. Methyllithium [917-54-4] and phenyllithium [591-51-5] are available in diethyl ether and cyclohexane—ether solutions, respectively, because they are not soluble in hydrocarbon solvents vinyllithium [917-57-7] and allyllithium [3052-45-7] are also insoluble in hydrocarbon solutions and can only be prepared in ether solutions (38,39). Hydrocarbon-soluble alkyllithium initiators are used directiy to initiate polymerization of styrene and diene monomers quantitatively one unique aspect of hthium-based initiators in hydrocarbon solution is that elastomeric polydienes with high 1,4-microstmcture are obtained (1,24,33—37). Certain alkyllithium compounds can be purified by recrystallization (ethyllithium), sublimation (ethyllithium, /-butyUithium [594-19-4] isopropyllithium [2417-93-8] or distillation (j -butyUithium) (40,41). Unfortunately, / -butyUithium is noncrystaUine and too high boiling to be purified by distiUation (38). Since methyllithium and phenyllithium are crystalline soUds which are insoluble in hydrocarbon solution, they can be precipitated into these solutions and then redissolved in appropriate polar solvents (42,43). OrganometaUic compounds of other alkaU metals are insoluble in hydrocarbon solution and possess negligible vapor pressures as expected for salt-like compounds. 

One 1-ml aliquot is added to 1.0 ml of freshly-distilled 1,2-dibromo-ethane (bp 132°C) in an oven-dried flask which contains a static atmosphere of nitrogen or argon. After the resulting solution has been allowed to stand at 25°C for 5 min, it Is diluted with 10 rat of water and titrated for base content (residual base) to a phenolphthalein endpoint with standard 0.100 M hydrochloric acid. The second 1-mL aliquot is added cautiously to 10 ml of water and then titrated for base content (total base) to a phenol phthalein endpoint with standard aqueous 0.100 M hydrochloric acid. The methyllithium concentration is the difference between the total base and residual base concentrations.2 Alternatively, the methynithiura concentration may be determined by titration with a standard solution of sec-butyl alcohol employing 2,2 -bipyridyl as an indicator. 

Trialkyls are only known as Lewis base adducts. Reaction of Au2Br6 with methyllithium at 70°C affords an unstable AuMe3 (which is probably AuMe3Br ), but stable phosphine adducts AuMe3PR3 (R, e.g. Me, Ph) can be made [169]. 

Mono- and l,3-di-ter/-butylcyclopentadienyllithium Li(Bu Cp) 4 (n = 1) and 5 (,n = 2) can be obtained directly by addition of methyllithium to 6,6-dimethyl fulvene and 2-/ert-butyl-6,6-dimethyl fulvene, respectively [27a]. Since the fulvenes themselves are easily accessible by base-induced condesation reactions [27b], this method offers a viable alternative to the usual metalation of the substituted cyclopentadienes 1 and 2 (Eq. 2). 

Reduction of nitrones such as N,a-diphenylnitrone 962 a with equivalent amounts of methyllithium/857 in HMPA/THF, again generating MesSili 1883, affords the corresponding Schiff bases such as 964a in 84% yield [82] (Scheme 7.25). 

Sulfoxides and sulfones are acylated in the a-position by aroyl- or acylimidazoles in the presence of methyllithium as base [100]... 

Azaallyl anion cycloadditions (13, 163).4 Nonstabilized 2-azaallyl anions (1) are readily generated by transmetallation of N-(trialkylstannyl)methylimines, prepared as shown in equation I, with a base such as butyl- or methyllithium. The... 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters.17 These can be prepared by hydroboration of an alkene with dibromobor-ane, followed by conversion of the dibromoborane to the cyclic ester. The homologation step is carried out by addition of methoxy(phenylthio)methyllithium to the boronate ester. The migration step is induced by mercuric ion. Use of enantioenriched boranes and boronates leads to products containing the groups of retained configuration.18... 

Formation of a-Sulfinyl carbanions has been widely investigated17. Several bases were found to be suitable for the generation of these species, e.g., methyllithium and lithium diisopropyl-amide. Butyllithium and rm-butyllithium, however, must be used with caution since they can cause cleavage of the carbon sulfur bond, resulting in an exchange of the ligand at sulfur by a nucleophilic displacement28-29. This method has been used for the preparation of optically active alkyl methyl sulfoxides 28. 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

The N-2 atom in l,2-dihydro-l-methyl-2,3,l-benzodiazaborine can easily be methylated by DMS in the presence of potassium hydroxide. This base is not sufficiently strong to be used in (V-alkylation of the nitrogen in benzo fused l,2-dihydro-l,2-azaborines in this case organolithium compounds can be employed. By successive treatment of (177 R = H) with methyllithium and an alkyl halide a number of A-alkyl derivatives have been prepared. 

Methyllithium Ammonia (stronger base) (stronger acid pka = 36)... 

Again for synthetic applications, thio- and dithioesters are particularly useful. Their enethiolates are easily generated [120]. Potassium and lithium amides and LDA can be conveniently used, and deprotonate the dithioesters quantitatively in THF at -78°C. Methyllithium under the same conditions also acts as a base and not as a nucleophile, and it has the advantage that its conjugate acid is the totally inert methane. 

A study investigated the use of various bases, such as potassium hydroxide, potassium tert-butoxide, sodium methoxide, methyllithium, rrrf-butyllithium, sec-butyllithium, phenyllithium, lithium diisopropylamide, and lithium hcxamethyldisila/anidc over a temperature range of — 78 to 80°C in the dehydrofluorination of 2-(fluoromethoxy)-l,l,l,3,3,3-hexafluoropropane to give 2-(fluoromethoxy)pentafluoropropene.28... 

The procedures described have been carefully designed so that base-free metal alkyls are not present except in the final purification stages when they are isolated. None of the intermediates is pyrophoric (except methyllithium if it is driedfrom solvent) so that the risk offire is minimal if a breakage should occur during the syntheses. 

An especially important example is that of 1,3-cyclopentadiene, which is acidic because its conjugate base (cyclopentadienide anion) is greatly stabilized by electron delocalization. The anion is formed easily from the hydrocarbon and methyllithium ... 

Two electrostatic potential maps, one of methyllithium (CH3Li) and one of chloromethane (CH3C1) are shown. Based on their polarity patterns, which do you think is which ... 

Acetylcyclohexanol has been prepared by the hydrolysis of 1-bromo-l-acetylcyclohexane3 and of 1-acetoxy-l-acetylcyclo-hexane oxime,7 by the hydration of 1-ethynylcyclohexanol,4 6 8 9 and by the treatment of 1-hydroxycyclohexanecarboxylic acid with methyllithium.10 The present procedure is based on that of Stacy and Mikulec for 1-acetylcyclopentanol.6... 

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