Butyllithium-potassium tert-butoxide

Alkenes lacking hydrogen atoms at allylic positions are much less acidic than ordinary unsaturated hydrocarbons. Superbases regioselectively exchange allylic protons in alkenes whenever there is a choice. However, a few examples of metallation of alkenic C-H bonds with superbases are known and a compilation of them is reported in Table 1. Ethylene itself has been deprotonated by the superbasic mixture constituted by butyllithium, potassium tert-butoxide, and TMEDA.41... 

Sabinene was obtained from (-)-a-thujene using /f-butyllithium-potassium tert-butoxide for the metalation. The unreacted (-)-a-thujene can be easily separated from (+)-sabinene. 

The S n2 reaction product, p-aminoesters 372, produced from the reaction of allyl bromide 371 and arylamine by treatment with triethylamine, could be converted into substituted p-lactams in the presence of base. Conventional bases such as ethylmagnesium bromide, -butyllithium, potassium tert-butoxide, lithium hydroxide and potassium hydroxide used in such cyclizations failed to give p-lactam 373. However, Sn[N(TMS)2]2 as a base in the cyclization of p-aminoesters could successfully cyclize 372 to give p-lactam 373 (Scheme 4.120). Under optimized cyclization conditions, it was found that 1.5 equiv. of Sn[N(TMS)2]2 in toluene under reflux for 6 h achieved the best yield (up to 83%.)... 

Introduction. The -butyllithium/potassium tert-butoxide reagent (n-BuLi/t-BuOK LIC-KOR Schlosser base) consisting... 

The n-butyllithium/potassium tert-butoxide mixture is immensely more powerful than butyllithium alone, and offers the possibility of functionalizing whole families of otherwise inert hydrocarbons. What should not be overlooked, however, is the fact that the chemical potential of the so-called superbase is attenuated when compared to butylpotassium. Thus, a manifold of aromatic, benzylic, and allylic organometallic intermediates can be generated in an ethereal medium under particularly mild and hence optimally selective conditions. The symbiotic action of two different metals obviously suppresses erratic side reactions without diminishing too much the deprotonation power of the superbasic reagent. 

Table 1 Metalation of alkenes with n-butyllithium/potassium tert-butoxide...

Table 2 Metalation of conjugated n-butyllithium/potassium tert-butoxide and homoconjugated dienes with...

Metalation of aUylsilanes with n-BuLi/t-BuOK shows good levels of y-selectivity (attack on the unsubstituted terminus of the aUyhnetaUic moiety). Increasing steric hindrance on silicon leads to a higher y-selectivity with perfect -stereocontrol. Good levels of a-selectivity are obtained only when the y-position is substituted and the electrophile is not sterically hindered. Examples of n-butyllithium/potassium tert-butoxide metalations of aUylsilanes are shown in Table 3. 

A few n-butyllithium/potassium tert-butoxide metalations of vinylic C-H bonds are known. For example, the metalation of ethene itself, or of l,7,7-trimethylbicyclo[2.2.1]hept-2-ene. 

Heteroelements in general facilitate metalation reactions. A-Methylpiperidine and, by extension, trimethylamine react smoothly with the 5ec-butyllithium/potassium tert-butoxide (LIS-KOR) mixture at their methyl groups. The same happens when... 

The first investigations in the 1960s [11,12] established the base-induced isomerization of alkyne precursors as the most practical and general route for the synthesis of alkoxy-and aryloxyallenes. In the meantime, a number of monosubstituted allenes 8 bearing an achiral or a chiral group R is smoothly accessible by this efficient procedure (Scheme 8.5) [1, 2,13-19]. Beside the most commonly used base potassium tert-butoxide, other bases, e.g. n-butyllithium, are also applicable for this isomerization. Recently, the yields of alkyne-allene isomerizations could be significantly increased, in particular with aryloxy-substituted allenes, by using microwave irradiation (Eq. 8.1) [20]. 

When treated with a strong base such as butyllithium or potassium tert-butoxide, 2-isocyano-tV[(S)-l-phenylethyl]propanamide (1) forms an enolate 2 which is not alkylated at low temperatures. Instead it rearranges on warming and cyclizes to give the enolate of 3,5-dihydro-5-methyl-3-[(,3 )-1-phenylctbylJ-4//-imidazol-4-onc (3) which can be alkylated with benzylic halides with excellent diastereoselectivities4,13. 3-Halopropenes or haloalkanes give much lower diastereoselectivities. 

R. The use of butyllithium in tetrahydrofuran or ether-hexane affords the triene 1n only 50-60% yield. When the ylide was generated with sodium hydride or potassium tert-butoxide in dimethyl sulfoxide by the submitter, the Wittig reaction gave triene containing 10-20% of the Z isomer. Part C illustrates the selective hydroboration of a diene with disiamylborane.1 The reaction is best carried out by adding preformed disiamylborane to the triene. Lower yields of homogeraniol were obtained by the submitter when the triene was added to the borane reagent. 

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 optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

This procedure consists of the synthesis of a precursor, methoxymethyl vinyl ether, an a-hydroxy enol ether, and the intramolecular hydrosilylatlon of the latter followed by oxidative cleavage of the silicon-carbon bonds. The first step, methoxymethylation of 2-bromoethanol, is based on Fujita s method.7 The second and third steps are modifications of results reported by McDougal and his co-workers. Dehydrobromination of 2-bromoethyl methoxymethyl ether to methoxymethyl vinyl ether was achieved most efficiently with potassium hydroxide pellets -9 rather than with potassium tert-butoxide as originally reported for dehydrobromination of the tetrahydropyranyl analog.10 Potassium tert-butoxide was effective for the dehydrobromination, but formed an adduct of tert-butyl alcohol with the vinyl ether as a by-product in substantial amounts. Methoxymethyl vinyl ether is lithiated efficiently with sec-butyllithium in THF and, somewhat less efficiently, with n-butyllithium in tetrahydrofuran. Since lithiation of simple vinyl ethers such as ethyl vinyl ether requires tert-butyllithium,11 metalation may be assisted by the methoxymethoxy group in the present case. 

NaNHR, or NaNR2. Lithium dialkylamides also react with aryl halides to give the A-arylamine. With these reagents, the benzyne mechanism generally operates, so cine substitution is often found. The reaction of an amine, an aryl halide, and potassium tert-butoxide generates the A -aryl amine. A -Arylation was accomplished with butyllithium and a secondary amine using Ni/C-diphenylpho-sphinoferrocene (dppf). Ring closure has been effected by this type of reaction, as in the conversion of 16 to the tetrahydroquinoline. 

Crotylboronic esters (2-butenylboronates) are thermally stable and isolable compounds at room temperature and undergo nearly quantitative additions to aldehydes. The required crotylboronic esters may be prepared by reaction of the crotyl potassium reagents derived from cis- or trans-2-butene with n-butyllithium and potassium tert-butoxide followed by addition of the appropriate trialkyl borates. ... 

The base-induced monodehydrochlorination reaction was originally introduced as the second step of a convenient two-step synthesis of methylenecyclopropanes from alkenes. The first step involves carbene-type cyclopropanation of the alkene with a 1,1-dichloroalkane and either butyllithium or sodium bishexamethyldisilazanide as the base. The dehydrochlorination is then carried out by reacting the intermediate 1-alkyl-1-chlorocyclopropane with potassium tert-butoxide in dimethyl sulfoxide. For ordinary unhindered chlorocyclopropanes this procedure gives from about 60% to nearly quantitative yields of products (Table 1). The ready availability of the starting materials and reagents makes the base-induced dehydrochlorination a most useful 1,2-elimination reaction for preparation of methylenecyclopropanes. The procedure is illustrated by the synthesis of l,l-dimethyl-2-methylenecyclopropane (3) from 2-methylpropene ( ) ... 

Alkynes react with various dichlorocarbene reagents to give 3,3-dichlorocyclopropenes 1, which can be hydrolyzed to cyclopropenones 2 in situ. The carbene reagents used are (A) chloroform, 50% sodium hydroxide, and triethylbenzylammonium chloride (TEBAC) (B) (bromo-dichloromethyl)phenylmercury (C) chloroform and potassium tert-butoxide and (D) chloroform and butyllithium. Although the yields of these reaction generally do not exceed 20%, a variety of cyclopropenones have been prepared by this method. The yields of biscyclo-propenones from diynes are very low. 

Treatment of the phosphine resin 33 with alkyl bromides, e.g. 34, gave the corresponding phosphonium bromide 35 in excellent yields. The formation of the phosphorane was described as a cmdal step, for which the transport of the base to the phosphonium site within the polymer was essential. Various bases, such as sodium hydride, potassium tert-butoxide in THF, and n-butyllithium in dioxane, have been employed. Good results for the formation of the ylide were obtained with a mixture of sodium methoxide, methanol, and THF, and more recently with sodium bis(trimethyl)silylamide in THF [34, 35]. After the addition of aldehyde 36... 

Such deprotonations may be achieved with Schlosser s super base , a combination of butyllithium and potassium tert-butoxide, MSgCOK (Bu OK). This reagent is even more basic than organolithium species. 

Reactions of the Lochmann base (a mixture of butyllithium with potassium tert.-butoxide in pentane [195]), with conjugated polyenes yield fully delocalized carbanions in high yield at a high rate [196]... 

Later work elaborating on the chemistry of glycals demonstrated the ease of formation of 1-stannyl glycals. These compounds, introduced in Scheme 3.1.1, are useful substrates for the direct formation of C-glycosides as well as for metal-metal exchanges with lithium to be discussed later in this chapter. As shown in Scheme 3.1.3, Hanessian, eta/.,4 utilized potassium tert-butoxide and butyllithium to effect the formation of 1-stannyl glycals. 

A solution of 0.12 mol of butyllithium in 78 ml of hexane is placed in the flask. Pentane or hexane (60 ml) is added, after which the solution is cooled to — 20 °C. Finely powdered potassium tert-butoxide (0.14 mol, 15.7g, powdering should be carried out in a dry atmosphere, preferably under inert gas) is added and the mixture is stirred for 30 min at 0°C. The fine suspension is then cooled to — 45 °C and... 

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