TMEDA 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. 

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. 

According to the principle of least nuclear motion [45] aromatic deprotonation should be faster than benzylic metalation, because the benzylic carbanion is expected to rehybridize slightly toward sp2 to achieve stabilization by conjugation with the aromatic n system. This is, in fact, often observed [217, 401, 423-425], but with some substrates benzylic metalation can effectively compete with aromatic metalation[181, 425, 426] (Scheme 5.47). Thus, treatment of toluene with BuLi/TMEDA or BuLi/DABCO at 80 °C for 0.5 h or with BuLi/KOtBu in Et20 at -20 °C for 4 h leads to clean formation of benzyllithium [85, 427, 428], The kinetic preference for aromatic deprotonation, because of the principle of least nuclear motion, thus seems to be too weak to control the regioselectivity of deprotonations in all instances. 

Remarkably, the closely related benzyllithium 304 is configurationally unstable even at -78 °C.138 Transmetallation of 303 (88% ee) at -78 °C gave an organolithium which reacted to give racemic product 305 in the presence or absence of TMEDA. Furthermore, the reaction of the 304-(-)-sparteine complex with each of racemic or enantiomerically pure 2 in a Hoffmann test gave the same 1 1.6 ratio of diastereoisomers. It is not yet clear whether this unexpected difference between 301 and 304 is due to an electronic difference between the naphthyl and phenyl systems, or whether it arises from the difference in steric hindrance, and therefore the dihedral angle between the ring and the amide, in the two compounds. 

The benzophenonedilithium compound 50, formed by reduction of benzophenone with lithium metal, crystallizes as a dimer (69). The four lithium atoms in the structure are divided into two different sets. The two benzophenone moieties are bridged, through the carbonyl oxygen atoms, by two symmetry-equivalent lithium atoms. Each of the two other lithiums is bonded to one phenyl ring and the ketone functionality reminiscent of that observed in benzyllithium (29), dilithiodibenzyl ketone (42), and dilithiodibenzylacetylene (49). The two different types of lithium atoms are complexed further to THE and TMEDA. 

After treating mc-2 with tert-butyllithium, both benzyllithium compounds (1-3)2 and m-3-TMEDA could be crystalhzed at -30 °C and subjected to X-ray structure analysis (Scheme 1). 

The HOMO of -3 TMEDA, showing a pyramidalized carbanionic unit, was visualized (Fig. 5) and compared with the HOMO of the benzyllithium compound (I ,S)-8, which displays a planar carbanionic unit. Whereas the planar system (R,S)-S reacts under inversion, in the case of the pyramidal system m-3-TMEDA retention of configuration should be expected. 

A dimer (58) of a-lithiated 2,6-dimethylpyridine crystallizes with TMEDA solvation. This dimer is completely unlike the polymeric benzyllithium (53) in that no T) -intramolecular bonding is observed. The centrd core of the dimer (58) consists of an eight-membeied ring formed from two intermolecular chelated Li atoms and nearly ideal perpendicular conformations of the a-CHaLi groups. Dimer (58) is a relatively rare example of a lithiated ir-system where Li exhibits only one carbon contact. 

A mixed Li /Mg+ aggregate corresponding to (213) is formed with either phenyl or methyl carbanions. An unusual lithium/magnesium acetylide is formed with stoichiometry Li2[(PhCsC)3Mg(TMEDA)]2 and is depicted as (214). The same authors also report the ion pair characterized as the mixed benzyllithium/magnesium TMEDA complex (215). ° A different mixed lithium/magnesium aggregate depicted as (216) is found for the THF-solvated anion of tris(trimethylsi-lyl)methyl carbanion. ... 

It should be noted that the crystal structure of the Li/TMEDA salt of benzyl phenyl sulfone reported by Boche is conceptually similar to the theoretical structure (122). X-Ray structure determination of a-(phenylsulfonyl)benzyllithium-TMEDA, a-(phenylsulfonyl)allyllithium and the potassium salt of bis(methylsulfonyl)-3-(2,6-dimethyoxypyridyl)sulfonylmeAane shows that the coordination about the anionic carbon atom is nearly planar, and that the p-orbital on the anionic carbon is approximately gauche to the two oxygen atoms on the sulfur. " The anionic caibon atom can be described as interacting with the sulfur atoms in an ylide-like manner with a hairier to rotation about the "C—SO2 bond. 

The preparation of benzyllithium from benzyl halides and alkyllithiums is not feasible because the benzyllithium initially formed reacts with the starting benzyl halides, producing 1,2-diphenylethane. Metalation of toluene with n-BuLi in the presence of TMEDA at 30 °C results in a 92 8 ratio of benzyllithium and ring metalated products. Metalation of toluene with n-BuLi in the presence of potassium rert-butoxide, and treatment of the resultant organopotassium compound with lithium bromide, affords pure benzyllithium in 89% yield. Alternatively, benzyllithiums are accessible by cleavage of alkyl benzyl ethers with lithium metal. " ... 

Di(phenylthio)methyllithium and di(phenylthio)benzyllithium, which are synthesized from the corresponding carbon acids and /i-butyllithium in THF, have been monoalkylated with primary but not with secondary alkyl halides. Higher homologs have not found widespread use because of the difficulties encountered in their alkylation. " The successful alkylation of such compounds has been achieved by carrying out the reactions in TMEDA (1 equiv.) in hydrocarbons (Scheme 55, entry c). Even the presence of THF with TMEDA almost completely suppresses the alkylation. However, double... 

It might be expected that in the presence of TMEDA or other tertiary diamines anomalous reaction products might be obtained with organolithium compounds such as benzyllithium. A number of reports in the literature disclose instances of the expected reaction products from reactions such as carbonation to the carboxylic acid and addition to benzophenone (I, 3, 4, 12). The phenyllithium-TMEDA (1 1) complex in benzene was allowed to react with benzophenone to give a 95% yield of triphenylcarbinol and with cyclohexanone to yield 59% of the 1-phenylcyclohexanol. The reaction with excess trimethylsilyl chloride is apparently quantitative. The main consideration in using these complexes is to use low temperatures for reaction and aqueous washes of ammonium chloride solution in the work-up to remove all of the tertiary diamine (the odor can be detected in low concentrations.)... 

Optimum Conditions for Preparing Benzyllithium from Toluene. Both the TMEDA and TED complexes of benzyllithium were investigated. Toluene metalation proceeds much faster than does benzene metalation under similar conditions. The benzyllithium complexes were more soluble in hydrocarbon solvents than were the corresponding phenyllithium complexes. This method of preparation of benzyllithium is the most convenient of the few literature procedures available. Other procedures described are the cleavage of benzyl methyl ether with lithium... 

The crystalline yellow 1 1 benzyllithium-TMEDA complex has a lower solubility in toluene than does the (benzyllithium )2-TMEDA complex which tends to form oils. Because of its higher solubility and to eliminate as much of the tertiary diamine as possible, the 2 1 complex was used for synthetic evaluations. It is probably the optimum ratio to use in this benzyllithium system. Solutions of up to 38 wt % benzyl-lithium in toluene or about 59 wt % of the (benzyllithium )2-TMEDA complex have been prepared. At ratios of 4 1 or more in toluene, a dark-red tar or oil also separated from the solution. With hexane as the solvent, yellow crystals of the 1 1 benzyllithium-TMEDA complex precipitated at a ratio of 2 1 or more, a dark-red oil separated instead. 

The toluene-metalation system in this study differs from that of Broaddus in that pure toluene was used as the solvent a RLi to TMEDA ratio of two was used. Analyses were usually run after complete reaction of the n-butyllithium unless otherwise noted. Higher reaction temperatures were used, and the final concentration of benzyllithium in solution was higher. 

The equilibration of the ring anions to the benzyl anion is the probable explanation, especially considering the recent work of Gau and our observation of an equilibration between m-xylene and toluene in the presence of (benzyllithium)2 TMEDA (20). (In fact, this type of system might be the basis of another route for a hydrocarbon acidity scale.) The more rapid disappearance of the ortho isomer, compared with the meta, may be the result of a possible intramolecular route for conversion to the benzyl anion. The meta and para isomers probably change to the benzyl anion by an intermolecular route that would be slower and agree with what was observed. Although complete resolution by GLC of the para and meta isomers was not done in this study, the para disappeared faster than the meta, but much slower than the ortho. In other time studies on the disappearance of the meta isomer at room temperature, about half the initial amount of this isomer was gone in three days and all of it in two to three months. 

Aging these benzyllithium solutions to remove the ring-isomer content is not practical in most cases, and use of large amounts of TMEDA to promote conversion can also cause problems later in synthetic use. Since heating the toluene product solution did not cause serious decomposition at 60 °C, this could provide a solution to the problem for most... 

Synthetic Application of (Benzyllithium —TMED A and Benzyl-lithium—TED. All the synthetic application studies were run with an aged (benzyllithium)2-TMEDA toluene solution that had 0.8% of the total organolithium compounds present as the tolyllithium isomers (only meta present) or with benzyllithium-TED crystalline complex free of ring isomers. 

The solutions of (benzyllithium )2-TMEDA were much more convenient to use than the solid, relatively insoluble benzyllithium-TED complex. The reaction yields vary between these two complexes. Whether this is a function of the different solvent systems used for each, lack of optimization, or the actual tertiary diamine present was not examined, however. 

Benzyllithium)2-TMEDA in Toluene. Trimethylsilyl chloride. Added trimethylsilyl chloride dissolved in ether at —5°C over 1 hr let... 

The principal monotrimethylsilyltoluene is the meta isomer. This agrees with the results of earlier experiments which find mainly m-lithio-toluene in the ring-lithiated byproducts in the synthesis of benzyllithium by lithiation of toluene with n-butyllithium-TMEDA (11, 12). On the basis of the current view that metalation of aromatic compounds proceeds... 

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