W-Butyllithium

The first proton to be removed from iV-methylpyrrole by w-butyllithium is from an a-position a second deprotonation occurs to give a mixture of 2,4- and 2,5-dilithiated derivatives. The formation of a 2,4-dilithio derivative is noteworthy since in the case of both furan and thiophene initial abstraction of a proton at C-2 is followed by proton abstraction from C-5 (77JCS(P1)887). iV-Methylindole, benzo[6]furan and benzo[6]thiophene are also deprotonated at C-2. Selenophene and benzo[6]selenophene and tellurophene and benzo[6]tellurophene similarly yield 2-lithio derivatives (77AHC(21)119). 

Pentyn-l-ol has been prepared from 4-penten-l-ol3 by bromi-nation followed by dehydrobromination with alkali,7 by the reaction of 3-bromodihydropyran with w-butylsodium or w-butyl-lithium,6 8 by the reaction of 2-methylenetetrahydrofuran with w-amylsodium or w-butyllithium,8 and by the method used in this preparation.9... 

Synthesis of 8,8-Bis(cyclopentadienyl)-7,9-bis(trimethylstannyl)-8-zirconabicyclo[4.3.0]nona-1 (9),6(7)-diene 109 (Scheme 7.31) [172] To a solution of bis(cyclopentadienyl)zirconium dichloride (585 mg, 2.0 mmol) in THF (10 mL) at — 78 °C was added dropwise a solution of w-butyllithium in hexane (2.4 mL, 4.0 mmol). After the reaction mixture had been stirred at — 78 °C for 1 h, a solution of l,8-bis(trimethylstannyl)-l,7-octadiyne (863 mg, 2.0 mmol) in THF (2 mL) was added at the same temperature. The temperature was then allowed to rise to ambient, and the mixture was stirred for a further 3 h. The solvent was then removed under reduced pressure and the product was extracted with toluene. The extracts were filtered and the filtrate was concentrated and kept at 0°C to afford the product 109 (723 mg, 55% yield). 

To this stirring mixture at ambient temperature was added w-butyllithium (0.32mL of a 2M solution in hexane) dropwise. The resulting solution was stirred at ambient temperature for 30 minutes. 

The submitter used a 1.24M solution of n-butyllithium in pentane obtained from Foot Mineral Co., and the checkers used a 1.45M solution of w-butyllithium in hexane obtained from Wako Pure Chemical Industries Ltd. (Japan). The nominal titer of active alkyl on the bottle agreed well with the value found by titration2 with 0.S0M (submitter) or 0.50JJ (checkers) solution of 2-butanol in xylene using 1,10-phenan-throline as indicator. 

Nearly quantitative generation of l,3-bis(methylthio)allyllithium was proved, as this solution yielded l,3-bis(methyIthio)propene (88-89%) and l,3-bis(methylthio)-l-butene (89%) by reaction with methanol and methyl iodide, respectively. The checkers found that lithium diisopropylamide can be replaced by w-butyllithium without any trouble for the generation of l,3-bis(methylthio)allyllithium, simplifying the procedure considerably at least in this particular case. Subsequent reaction with propionaldehyde gave l,3-bis(methylthio)-l-hexen-4-ol in 85% yield, and no appreciable amount of by-product, such as the addition product of w-hutyllithium with propionaldehyde or with the intermediate 1.3-bis(methylthio)propene, was formed. 

Reaction of l,3-bis(methylthio)-2-methoxypropane with 2 moles of lithium diisopropylamide5 (or w-butyllithium) effects (a) the elimination of methanol to form l,3-bis(methylthio)propene and (b) the lithiation of this propene to generate l,3-bis(methylthio)allyllithium in solution. Its conjugate acid, l,3-bis(methylthio)propene, can be regenerated by protonation with methanol, and has also been prepared (a) in 31% yield by reaction of methylthioacetaldehyde with the lithio derivative of diethyl methylthiomethylphosphonate,5 (b) in low yield by acid-catalyzed pyrolysis of l,l-bis(methylthio)-3-methoxypropane,6 and (c) in low yield by acid-catalyzed coupling of vinyl chloride with chloromethyl methyl sulfide.7... 

The w-butyllithium in hexane was purchased from Ventron Corp. 

Considerable evidence for the existence of a carbanion intermediate in the isotopic exchange reactions of p3U idine 1-oxides is available. Treatment of 4-chloro-3-methylpyridine 1-oxide (61), for example, with w-butyllithium gives an intermediate which reacts with cyclohexanone to give 62. In addition Tupitsyn et al. have found a linear... 

Ethyl pyridine-2-acetate and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with w-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

In our context, especially C-Li distances are of interest. A first successful Li- C REDOR study was undertaken in order to establish the structure of the previously discussed TMEDA complex of fluorenyllithium °, prepared from Li-enriched w-butyllithium and fluorene with at natural abundance. The REDOR pulse sequence used is depicted in Figure 20. The number of rotor cycles is increased in a symmetric fashion about the central jr-pulse in order to increase the dephasing time. 

In order to determine the strnctnres of the intermediate organolithium compounds, 1-phenylpropyne was metalated with 4 equivalents of w-butyllithium in refluxing cyclohexane . One hour later, no absorption due to lithiated phenylpropynes was detected. The IR spectrum showed only a strong peak at 1775 cm due to a trilithioallene, which gradually became much stronger. Apparently, the introduction of the first Li atom is much slower than subsequent lithiations, so no mono- and dilithiated species were observed in the IR spectrum. 

Benzyl thiol 70 was deprotonated using w-butyllithium in THF at room temperature, lithiated with DTBB (5%) at 0°C to give the benzyllithium 71 and then treated with electrophiles at temperatures ranging between —30 and 0°C. Final hydrolysis afforded the expected products 72 (Scheme 29 f. The reaction applied to allyl mercaptan failed, giving an intractable mixture of products. 

The tin-lithium exchange reaction does not play an important role for the generation of 1-halo-l-lithioalkenes. Whereas in a-bromoalkylstannanes tin-lithium exchange occurs upon treatment with n-butyllithium , the bromine rather than the tin is replaced against lithium, when a-bromovinylstannanes are allowed to react with w-butyllithium . 

In the group of Izod, the tris(phosphane oxide) 19 was 1,2-dilithiated by the reaction with two equivalents of w-butyllithium in THF at room temperature (Scheme 7). The similarity of the structural formula of compound 20 (Lewis formula) to 1,2-dilithium compounds found by Sekiguchi and coworkers (see Section n. E), where two lithium centres are bridging a C2 unit, is not maintained in the solid state. The X-ray structural analysis reveals a centrosymmetric dimer containing no carbon-lithium contacts (Figure 8). 

Korneev and Kaufmann successfully lithiated 2-bromo-l,l-diphenylethylene (46) by bromide-lithium exchange to form 2-lithio-l,l-diphenylethylene (47). A second lithia-tion could be effected in four hours at room temperature by deprotonation of the aromatic ring with w-butyllithium in the presence of TMEDA (Scheme 17). Like in the synthesis of compound 23, the first lithiation activates the ortho-hydrogen atom of the Z-phenyl substituent to give 1,4-dilithium compound 48. In total, three equivalents of the alkyl-lithium base are required the third equivalent is consumed in the trapping reaction of w-bromobutane with generation of octane. 

In the first step, when 49 was treated with two equivalents of w-butyllithium in a mixture of w-pentane and diethyl ether, the dilithiated dibenzylphosphane 50 was obtained as... 

Due to the formation of phenyUithium, the reaction of bis(phenyltelluriomethyl)silane 118 with w-butyllithium does not lead to the doubly lithiated compound 117a, but to the bis(butyltelluriomethyl)silane 119 and phenyUithium (Scheme 43) . 

For the hthiation reactions of the closely related compound 123 with w-butyllithium, a significant solvent effect was observed by Maercker and coworkers . While a two-fold lithiation process by tellurium-lithium exchange takes place in hexane, yielding highly pyrophoric 91, only a-deprotonation occurs when the reaction is effected in THF, yielding the monohthiated tellurole 124 (Scheme 45). 

By prior substitution at the a-carbon centre (deprotonation, followed by sUylation), also asymmetrically functionalized bis(lithiomethyl)silanes like compound 161 are accessible from their substituted parent compounds (e.g. compound 160). This selective reaction sequence is based on the possibility of deprotonating bis(phenylthiomethyl)silane 155f with w-butyllithium without attacking the thioether groups (Scheme 58). ... 

Synthetic cA-l,4-polyisoprene (structure 5.42) is produced at an annual rate of about 100,000 t by the anionic polymerization of isoprene when a low dielectric solvent, such as hexane, and K-butyllithium are used. But, when a stronger dielectric solvent, such as diethy-lether, is used along with w-butyllithium, equal molar amount of tra i -l,4-polyisoprene and cA-3,4-polyisoprene units is produced. It is believed that an intermediate cisoid conformation assures the formation of a cis product. An outline describing the formation of cA-1,4-polyisoprene is given in structure 5.42. 

To obtain complete conversion of ketones to enolates, it is necessary to use aprotic solvents so that solvent deprotonation does not compete with enolate formation. Stronger bases, such as amide anion ( NH2), the conjugate base of DMSO (sometimes referred to as the dimsyl anion),2 and triphenylmethyl anion, are capable of effecting essentially complete conversion of a ketone to its enolate. Lithium diisopropylamide (LDA), which is generated by addition of w-butyllithium to diisopropylamine, is widely used as a strong... 

An important complement to the Wittig reaction is the reaction of phosphonate carbanions with carbonyl compounds.151 The alkylphosphonate esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are more nucleophilic than an analogous ylide, and even when R is a carbanion-stabilizing substituent, they react readily with aldehydes and ketones to give alkenes. Phosphonate carbanions are generated by treating alkylphosphonate esters with bases such as sodium hydride, w-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.152... 

Dibromobutane (23.8 g., 0.11 mole) (Note 5) is injected into the addition funnel and then is added to the solution with stirring over a period of about 15 minutes. The funnel is rinsed by injection of 5 ml. of dry tetrahydrofuran, and the reaction is allowed to stir at —78° for 45 minutes. w-Butyllithium (55 ml.,... 

Unlike analogous reactions with a carbon nucleophile, the initial attack of the lithium amide was reversible. A strong piece of supporting evidence was the exclusive formation of the butyl addition product 504 when w-butyllithium was added after initial formation of the aza enolate 505 (Scheme 8.164). The reaction outcome is therefore heavily dependent on the secondary reaction with the... 

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