Phenyllithium deprotonation

With phenyllithium, the iminophosphoranes of benzoic acid hydrazides 157 can be deprotonated, as shown in Scheme 62.0-Acylation of the amide-enolates 158 affords intermediates 159, which are in turn cyclized by an aza-Wittig reaction to 1,3,4-oxadiazoles 160 (68JA5626). 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

Fluonnated ylides have also been prepared in such a way that fluorine is incorporated at the carbon p to the carbamomc carbon Various fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyllithium or lithium dusopropy-lamide did not lead to y hde formation, rather, deprotonation was accompanied by loss of fluonde ion However deprotonation with hydrated potassium carbonate in dioxane was successful and resulted in fluoroolefin yields of45-80% [59] (equation 54) p-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydride The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyllithium to form a new ylide, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [61] such as an acetylide to form a fluonnated enyne [62] (equation 56)... 

The ylide is prepared by deprotonating a triphenylalkylphosphonium salt with a strong base, commonly an organometallic base such as butyllithium or phenyllithium. The hydrogens on the carbon that is bonded to the phosphorus of the salt are somewhat acidic because the carbanion of the conjugate base (the ylide) is stabilized by the inductive effect of the positive phosphorus atom. In addition, a resonance structure with five bonds to phosphorus makes a minor contribution to the structure and provides some additional stabilization. The triphenylalkylphosphonium salt can be prepared by an SN2 reaction of triphenylphosphine with the appropriate alkyl halide (see Section 10.9). 

Kauffmann reported the first tellurium-lithium exchange reaction of a vinylic telluride with an organolithium compound.255 Phenyl vinyl telluride 168 was deprotonated by lithium dicyclohexylamide (LDCA) in THF, and the resulting vinyl anion 169 was reacted with chlorotrimethylsilane to give telluride 170. Vinylsilane telluroacetal 170 was then reacted with phenyllithium to give the corresponding vinyllithium, which was captured with chlorotrimethylsilane to give the bis-silylated ethane 171 (Scheme 96).255... 

Deprotonation of the hydroxyalkylpolysilanes la-lc with two or more equivalents methyllithium, rbutyllithium, or phenyllithium, respectively, leads to the trisilanes 6a-6e, which are formed by addition of the excess organolithium reagent to the polar Si=C-bond (Eq. 4). 

Zoltewicz and Helmick (665) found that, whereas pyrazine reacts with potassium amide to form the anionic o complex (20), methylpyrazine undergoes deprotonation to give the delocalized carbanion (21) and the p.m.r. spectrum shows that pyrazine with phenyllithium at —45° is converted completely into a dihydro adduct analogous to (20) (720a). 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

In contrast to the above described reactivity of dimethylsulfonium trimethylsilylmethylide (2), triphenylarsonium trimethylsilylmethylide (5) is able to cyclopropanate the C-C double bond of chalcone [( )-l,3-diphenylpropenone] and some of its derivatives. The arsonium ylide is prepared in situ from (trimethylsilylmethyl)triphenylarsonium tetraphenylborate (4) by deprotonation with phenyllithium. The reactions with various substituted chalcones were carried out at room temperature and at — 70 "C. Although the yields achieved for cyclopropanes 6 are almost equal, the formation of the -isomer predominates at lower temperature whereas at room temperature the isomer ratio is nearly 1 1. 

Oguni discovered that phenyllithium in the presence of 5 mol % of chiral Schiff base hgands created a stable and efficient catalyst system. The addition to cyclohexene oxide occurred in quantitative yield to form the phenylcyclohexanol in 90% ee (Scheme 11) [24]. Oguni proposed that deprotonation of the phenol and/or 1,2-addition to the imine ligand 15 formed the catalytically-active species. 

The driving force for the Br/Li exchange is probably much weaker in the case of phenyllithium, because the difference in base strength between PhLi and 3-thienyllithium is not large. On the other hand, the acidity of the 2-proton is sufficient to warrant a fast deprotonation by PhLi. 

The reactivity of the organolithium compounds is increased by adding molecules capable of solvating the lithium cations. Tetramethylenediamine (TMEDA) is commonly used for organolithium reagents. This tertiary diamine can chelate lithium. The resulting complexes generally are able to effect deprotonation at accelerated rates.In the case of phenyllithium, NMR studies show that the compound is tetrameric in 1 2 ether-cyclohexane, but dimeric in 1 9 TMEDA-cyclohexane. ... 

Reagents such as n-butyllithium, methyllithium, and phenyllithium manufactured by this process are commercially available. Carbanions can also be formed by an acid-base reaction involving heterolytic dissociation of a carbon-hydrogen bond by a strong base. An example is the deprotonation of limonene (86) by -butyllithium complexed with tetramethylethylenedia-mine (TMEDA), as shown in equation 5.61. Note that there is more than one kind of allylic proton in 86, but the deprotonation preferentially produces the least-substituted carbanion. ... 

Note the use of the shorthand notation for n.-butyllithium (BuLi) and for butane (BuH). In some cases, a powerful organolithium base such as tert-butyllithium (36) can deprotonate a compound that is not normally considered to be an acid benzene, for example. er -Butyllithium reacts with benzene to give the conjugate base phenyllithium (39), along with 2-methyl propane (the conjugate acid). 

Subsequent studies by Wittig demonstrated that deprotonation of benzyl alkyl ether derivatives with phenyllithium could provide the requisite carbanion and induce [1,2]-Wittig rearrangement. For example, treatment of benzyl methyl ether (9) with phenyllithium provided a-methyl benzyl alcohol (10) in 35% yield upon workup. 

Kinetics and reaction mechanism for CO2 exchange in 2-imidazolidinone-l-carboxyhc acid lithium salt (Li 20) were investigated by Lihs and Caudle [134]. N-Carboxyimidazolidone anion, 20, was probed as an analogue for N -carboxybiotin and synthesized as the lithium salt by deprotonation of 2-imidazolidone 21 with phenyllithium and further reaction of the resulting lithium amide with carbon dioxide. The study was addressed to ascertain the viability of unimolecular CO2 elimination from... 

An intramolecular cyclisation occurs when [Ru(n -C5H5)(CO)2(CH2-2-Br-C(5H4)] is o-deprotonated with butyllithiura followed by electrophilic attack by a tiimethyloxonium salt The metallaindene complex produced, [Ru(Ti -C5H5)(CO)(=C OMe)C6H4CH2-K-C,C,)], reacts with phenyllithium and trimethylsilyl triflate to produce [Ru(Ti5-C5H5)(CO)(=4r Ph)C6H4CH2-K-C,C,)] which was structurally characterised. 212... 

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