Butyllithium TMEDA in Hexane

3 Butyllithium, Complexed with Potassium firf-Butoxide in THF Apparatus Fig. 1, 500 ml Scale 0.10 molar 

A solution of 0.105 mol of butyllithium in 75 ml hexane is added to the flask by means of a syringe. The solution is brought to a temperature of —100 °C (occasional cooling with liquid nitrogen) and a solution of 0.105 mol (11.9 g) of 

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Upon treatment of 1,3-pentadiyne with excess n-butyllithium/TMEDA in hexane at room temperature another lithiocarbon C,Li. 157 is obtained as was the case with... 

Polycyclic Aromatics. Extensive replacement of hydrogen by lithium in polycyclic aromatic hydrocarbons has been demonstrated by Halasa (15). Anthracene, biphenyl, fluorene, indene, and ferrocene (16) undergo polymetalation by n-butyllithium—TMEDA in hexane at 70°C for 24 hours. The products are insoluble mixtures of polylithio compounds containing up to 10 lithium atoms per molecule. Derivatization was accomplished using both D20 and trimethylchlorosilane and by analyzing the mixture of deuterated or silylated products by mass spectrometry. The results for anthracene, which are typical, appear in Table I. 

For the deprotonation of less acidic precursors, which do not lead to mesomerically stabilized anions, butyllithium/TMEDA in THF or diethyl ether, or the more reactive, but more expensive,. seobutyllithium under these conditions usually are the most promising bases. Het-eroatomic substitution on the allylic substrate, which docs not contribute to the mesomeric or inductive stabilization often facilitates lithiation dramatically 58. In lithiations, in contrast to most other metalations, the kinetic acidity, caused by complexing heteroatom substituents, may override the thermodynamic acidity, which is estimated from the stabilization of the competing anions. These directed lithiations59 should be performed in the least polar solvent possible, e.g.. diethyl ether, toluene, or even hexane. 

Phenylthio-l-trimethylsilylalkanes are easily prepared by the alkylation of (phenylthioXtrimethylsilyl)mcthane as shown in Scheme 10 [40], The treatment of (phenylthio)(trimethylsilyl)methane with butyllithium/tetramethylethylene-diamine (TMEDA) in hexane followed by the addition of alkyl halides or epoxides produces alkylation products which can be oxidized electrochemically to yield the acetals. Since acetals are readily hydrolyzed to aldehydes, (phenylthioXtrimethylsilyl)methane provides a synthon of the formyl anion. This is an alternative to the oxidative transformation of a-thiosilanes to aldehydes via Sila-Pummerer rearrangement under application of MCPBA as oxidant [40, 41]. 

A more versatile approach to 4,7-disubstituted dihydroacepentalenes 65 is via the stable acepentalene dianion 64 as an easily accessible intermediate. Dipotassium acepentalenediide 64 can be obtained in virtually quantitative yield by treatment of triquinacene 10 with the superbasic mixture of potassium f-pent-oxide and butyllithium [or even better potassium f-butoxide, butyllithium and tetramethylethylenediamine (TMEDA)] in hexane, the so-called Lochmann-Schlosser base (Scheme 15) [62, 63]. Mechanistically this transformation has... 

The cyclic acetal 3 with an axial phenyl group, but not its equatorial epimer, can be deproto-nated by the use of butyllithium and TMEDA in hexane (not in THF) to 3-Li and stereospecif-ically deuterated to 431. 

Butyllithium, Complexed with Sodium- or Potassium f-Butoxide and TMEDA in Hexane or Pentane... 

The classical example of a coordination-induced orfJio-lithiation is the reaction of PhCH2N(CH3)2 with butyllithium [1], giving o-Li—C6H4—CH2N(CH3)2. With BuLi t-BuOK in a mixture of THF and hexane the only reaction is a-metallation [2/3], while BuLi TMEDA in hexane gives rise to both ring- and a-lithiation [2]. 

However, when vinylic metalation is desired, competing allylic deprotonation may occur. In general, thermodynamic acidity and the kinetic preference for vinylic deprotonation of cyclic alkenes decrease with increasing ring size." The stable alkane-soluble reagent n-Butyllithium-Potassium t-Butoxide-TMEDA in hexane metalates Ethylene with potassium and effects selec-... 

Competitive metallation experiments with IV-methylpyrrole and thiophene and with IV-methylindole and benzo[6]thiophene indicate that the sulfur-containing heterocycles react more rapidly with H-butyllithium in ether. The comparative reactivity of thiophene and furan with butyllithium depends on the metallation conditions. In hexane, furan reacts more rapidly than thiophene but in ether, in the presence of tetramethylethylenediamine (TMEDA), the order of reactivity is reversed (77JCS(P1)887). Competitive metallation experiments have established that dibenzofuran is more easily lithiated than dibenzothiophene, which in turn is more easily lithiated than A-ethylcarbazole. These compounds lose the proton bound to carbon 4 in dibenzofuran and dibenzothiophene and the equivalent proton (bound to carbon 1) in the carbazole (64JOM(2)304). 

Furan reacts with butyllithium in boiling diethyl ether to yield 2-lithiofuran, and further lithiation at C-5 occurs when this product is treated with a second equivalent of the reagent in hexane containing MMA, // -tetramethylethane-1,2-diamine (TMEDA) (Scheme 6.26a). 

Butylpotassium and butylcesium deprotonate furan at the 2-position (75BSF1302), but butyllithium is the reagent of choice. When furan is treated with butyllithium the reactions in Scheme 114 occur (77JCS(P1)887>. The conditions, however, may be controlled to yield predominantly the mono- or the di-lithio derivative. By carbonation and esterification of the reaction mixture obtained by treatment of furan with butyllithium and TMEDA (1 1 1) in ether at 25 °C for 30 min, a 98% yield of methyl furan-2-carboxylate is obtained. Similarly, a butyllithium TMEDA furan ratio of 2.5 2.5 1 in boiling hexane for 30 min results in 91% of dimethyl furan-2,5-dicarboxylate and 9% of the monoester. Competition experiments indicate that furan reacts with butyllithium faster than thiophene under non-ionizing conditions but that the order is reversed in ether or in the presence of TMEDA. 

Lithium hydride,1 LiH. Commercially available LiH is essentially inert as a me-tallation reagent. A highly reactive form of LiH can be prepared by hydrogenation of butyllithium in the presence of TMEDA (1-1.2 equiv.) in hexane at 30-35°. No reaction is observed in the absence of TMEDA. This material metallates dibenzyl ketone almost instantly at 25°. 

Deprotonation of bicyclobutane (47) by n-butyllithium in hexane containing a slight excess of TMEDA, followed by solvent evaporation, filtration and recrystallization from benzene yields the dimeric, bis-chelated aggregate (48). Hiis aggregate corresponds exactly to structural type (16). It is perhaps surprising that many more examples of aliphatic carbanions have not yet been characterized with this general bis-chelated dimeric structure. 

Controlled dilithiation of propyne can be achieved by using two equivalents of n-butyllithium in hexane/ether in the presence of one equivalent of TMEDA... 

Dilithiation of 1 - and 2-alkynes with n-butyllithium can be achieved already at room temperature by using diethyl ether as the solvent instead of hexane 3-Alkynes, however, under these conditions yield only monoanions. On the other hand up to four lithium atoms could be introduced into 1,8-cyclotetradecadiyne with n-butyllithium in THF or in the presence of TMEDA even in hexane as the solvent... 

Bromobutane. Added 1-mole equivalent TMEDA to 11.4% sec-butyllithium in hexane at 0°C, heated to 50°C for 1 hr and then cooled to 0°C added 1-mole equivalent 2-bromobutane over 20 min let warm over 0.5 hr worked up hydrolyzed distilled bp 52°C (2.9 mm) 33%, N- (2-methylbutyl) -N,N N -trimethyl-l,2-ethanediamine. 

The metallation of 1-methylpyrrole proceeds considerably less easily than that of thiophene and furan. With the butyllithium TMEDA complex in hexane, however, this pyrrole derivative can be lithiated in a short time. Since THF is attacked very readily by BuLi TMEDA, it cannot be used as a co-solvent during the metallation. It is added when the metallation in hexane is complete. 

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