Benzyllithium

The easiest access to most benzyllithium, -sodium, or -potassium derivatives consists of the deprotonation of the corresponding carbon acids. Hydrocarbons, such as toluene, exhibit a remarkably low kinetic acidity. Excess toluene (without further solvent) is converted into benzyllithium by the action of butyllithium in the presence of complexing diamines such as A. Af.Af.jV -tetramethylethylenediamine (TMEDA) or l,4-diazabicyclo[2.2.2]octane (DABCO) at elevated temperatures1 a procedure is published in reference 2. 

Dibenzylamino)-3-phenylpropanal adds benzyllithium reagents with virtually complete steric approach controlled selectivity again the simple diastereoselectivity is poor (approx. 1 11 2)5. 

Organolithium reagents in which the carbanion is delocalized are more useful than alkyllithium reagents in alkylation reactions. Allyllithium and benzyllithium reagents can be alkylated and with secondary alkyl bromides and a high degree of inversion of configuration is observed.78... 

The reactions of a benzylzinc chloride TMEDA adduct with either benzyllithium or benzyl(trimethylsilyl)lithium TMEDA adduct yielded both homoleptic dibenzylzinc (37, Figure 16) and heteroleptic monobenzylzinc compounds as TMEDA adducts. The heteroleptic diorganozinc compounds do not disproportionate as long as TMEDA is present, but removal of the chelating nitrogen ligand in the gas phase does cause disproportionation. 

Another system that has been investigated by C CP/MAS NMR spectroscopy as a function of different ligands is a-(dimethylamino)benzyllithium (2, Scheme 1) . The DEE complex was proven to exist in the solid state as an rf coordinated dimer . All the studied complexes are of an tf type according to comparison to solution NMR data. However, the actual structure varies as reflected by the shift difference between the two orf/zo-carbons. This difference ranges from 4.4 ppm for the N, N, N, N, N"-pentamethyldiethylenetriamine (PMDTA) complex to 20.3 ppm for the TMEDA complex. 

These aspects have been investigated for a number of substituted benzyllithium systems—Q -(phenylthio)benzyllithium (3), a-phenyl-a-lithiodithiane (4) and a-trimethylsilyl... 

Standard organolithium reagents such as butyllithium, ec-butyllithium or tert-butyllithium deprotonate rapidly, if not instantaneously, the relatively acidic hydrocarbons of the 1,4-diene, diaryhnethane, triarylmethane, fluorene, indene and cyclopentadiene families and all terminal acetylenes (1-alkynes) as well. Butyllithium alone is ineffective toward toluene but its coordination complex with A/ ,A/ ,iV, iV-tetramethylethylenediamine does produce benzyllithium in high yield when heated to 80 To introduce metal into less reactive hydrocarbons one has either to rely on neighboring group-assistance or to employ so-called superbases. 

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 naphthalene-catalyzed (2.5%) lithiation of phthalan 330 (or its substituted derivatives ) in THF at room temperature allowed the preparation of the functionalized benzyllithium intermediate 331, which reacted with electrophiles at —78°C to give, after hydrolysis, the corresponding functionalized benzyl alcohols 332 (Scheme 97). When carbon dioxide was used as the electrophilic reagent, the corresponding 5-lactone was directly obtained . When carbonyl compounds were used as electrophiles, the cyclization of the resulting products 332 under acidic conditions (85% H3PO4) allows the synthesis of substituted isochromans. 

The state of aggregation of RLi in various solvents has been investigated by a variety of methods. In 1967, West and Waack used a differential vapor pressure technique to study solution colligative properties of RLi . Deviations from ideality indicated that in THF at 25 °C, MeLi and BuLi are tetrameric, PhLi dimeric and benzyllithium monomeric. MeLi was also suggested to be tetrameric in diethyl ether. 

An efficient kinetic resolution was also observed during the (—)-sparteine-mediated deprotonation of the piperidin-2-yhnethyl carbamate rac-112 (equation 25). By treatment of rac-112 with s-BuLi/(—)-sparteine (11), the pro-S proton in (/ )-112 is removed preferentially to form the lithium compound 113, which undergoes intramolecular cyclo-carbolithiation, and the indolizidinyl-benzyllithium intermediate 114 was trapped with several electrophiles. The mismatched combination in the deprotonation of (5 )-112, leading to cp/-113, does not significantly contribute to product formation. Under optimized conditions [0.75 equivalents of s-BuLi, 0.8 equivalents of (—)-sparteine, 22 h at —78°C in diethyl ether] the indolizidine 115 was isolated with 34% yield (based on rac-112), d.r. = 98 2, e.r. = 97 3 optically active (5 )-112 was recovered (46%, 63% ee). 

Beak and coworkers found the (—)-sparteine-complex of iV-Boc-Af-(p-methoxyphe-nyl)benzyllithium 244, obtained from 243 by deprotonation with n-BuLi/(—)-sparteine (11) in toluene, to be configurationally stable (equation 57) . On trapping 244 with different electrophiles, the substitution products 245 are formed with high ee. Efficient addition reactions with imines and aldehydes have also been reported. The p-methoxyphenyl residue is conveniently removed by treatment with cerinm ammoninm nitrate (CAN). 

The closely related a-(pyrid-2-ylthio)benzyllithium (257) has a higher configurational stability, and equilibration with the chiral ligand prior to the substitution step is required , indicating that a dynamic thermodynamic resolution is important (equation 61). Depending on the method of calculation, (7 )-257 255b was found to be by 1.42 to 1.92 kcalmoD ... 

The authors assume that the halides react with stereoinversion, whereas the tosylates prefer suprafacial attack due to binding interaction with the lithium ion in the transition state . A comparable dependence of the stereochemical course from the leaving group has been observed in other stereodefined benzyllithiums, too . The addition of 268 to A-methyl-benzylideneimine proceeds with only low yield . ... 

Since carbohthiations usually proceed as syn additions, 458 is expected to be formed first. Due to the configurationally labile benzylic centre it epimerizes to the trani-substitu-ted chelate complex epi-45S. The substitution of epi-458 is assumed to occur with inversion at the benzylic centre. Sterically more demanding reagents (t-BuLi) or the well-stabilized benzyllithium do not add. The reaction works with the same efficiency when other complexing cinnamyl derivatives, such as ethers and primary, secondary, or tertiary amines, are used as substrates . A substoichiometric amount (5 mol%) of (—)-sparteine (11) serves equally well. The appropriate (Z)-cinnamyl derivatives give rise to ewf-459, since the opposite enantiotopic face of the double bond is attacked . 

The carbolithiation of styiyl carbamates such as 486 by alkyllithium/(—)-sparteine (11) leads to configurationally stable benzyllithium compounds 487, which have been further substituted by electrophiles (equation 133) °. However, only low enantioselectivities could be achieved with (—)-sparteine (11) (e.r. = 70 30) or (—)-o -isosparteine (14) (e.r. ... 

This is illustrated by the capricious behavior of a benzyllithium derivative with known configuration discussed in Section 1.1.1.2.1.1.1.12. 

In regard to this latter point, Cubbon and Margerison noted (31) that adding n-butyllithium to toluene led to the formation of solutions which "developed a yellow-orange color.") If the spectrum of benzyllithium in toluene in the presence of anisole resembles that in benzene where the X max is reported (32,33) to be 292 nm, the decay in absorbance with time noted (13) at 330 nm may be attributable to transmetallation involving toluene rather them the foregoing aromatic ethers. 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

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