TMEDA phenyllithium

Phenyllithium in ether adds to pyridazine and 6-substituted pyridazines at position 3. By using TMEDA, addition at position 4 is strongly promoted (78RTC116). 

In the case of phenyllithium, it has been possible to demonstrate by NMR studies that the compound is tetrameric in 1 2 ether-cyclohexane but dimeric in 1 9 TMEDA-cyclohexane. X-ray crystal structure determinations have been done on both dimeric and tetrameric structures. A dimeric structure crystallizes from hexane containing TMEDA. This structure is shown in Fig. 7.1 A. A tetrameric structure incorporating four ether molecules forms from ether-hexane solution. This structure is shown in Fig. 7.IB. There is a good correspondence between the structures that crystallize and those indicated by the NMR studies. 

TMEDA changes into the dimeric [PhLi(TMEDA)]2. Monomeric phenyllithium PhLi(PMDTA) is observed if the tridentate donor ligand PMDTA (PMDTA = N,N,N, N, N"-Pentamethyldiethylenetriamine) is utilized.13... 

Donor-containing phenyllithium derivatives display a variety of structural modes, as seen for the tetrameric [PhLi(OEt2)]4 62,70 the dimeric [PhLi(TMEDA)]2 63,71 and the monomeric [PhLi(PMDTA)] 64,72 clearly demonstrating the structure-determining role of the donor. 

In the solid state NMR study, uncomplexed phenyllithium, assumed to be a tetramer, as well as the TMEDA complexed dimer and the PMDTA complexed monomer were investigated. Both Li and Li isotopes were used in the preparations. The C spectra of the complexes are presented in Figure 12. It is evident that the substitution of Li with Li has profound effects on the Unewidths, especially of the ipso-carbon at ca 180 ppm in the aggregated uncomplexed system (Figure 12a and 12b, respectively). This is in accordance with the previously mentioned study of methyllithium. However, even the other positions are affected by the dipolar couplings to the four quadrupolar lithium cations, but to a lesser extent due to the larger C-Li distances. 

Data from Reference 132 (60 MHz) for butyllithium-pyridine adducts (in Et20) and Reference 134 (100 MHz) for phenyllithium-pyridine adducts (in TMEDA). b Very broad signal. c — indicates data do not exist. 

In 1969 Giam and Stout reported the first isolation of solid organolithium adducts of pyridine.134 In a typical experiment pyridine was added to a cold LiBr-free ether solution of phenyllithium. The resulting yellow solid was collected and investigated by 100 Hz H-NMR spectroscopy (Table XIV) in N,N,N. /V -tetramethyI-l,2-diaminoethane (TMEDA) solution. It was assigned structure 86. The solid was sensitive to moisture, oxygen, and heat, and when dissolved in diethyl ether it was oxidized by oxygen to afford... 

By the action of phenyllithium, pyridazine is converted to adduct 100 (Table XVI), resulting from nucleophilic attack at position 3.34 The structural assignment is based upon H- and 13C-NMR, starting with pyridazine and its 4,5-dideutero derivative. The site of attachment of the phenyl group is other than that observed with the amide ion in ammonia (C-4). Analysis of the products obtained after hydrolysis and oxidation indicates the presence of nearly 5-6% of 4-phenyIpyridazine. Although this finding implies the formation of a small amount of the isomeric adduct 101, there is no NMR evidence for it. However, both isomeric adducts can be detected when the reaction is carried out in the presence of TMEDA or tetrahydrofuran at a lower temperature. The chemical shift values of adduct 101 are closely similar to those of the amino analog 29. 

The reaction of pyrazine with phenyllithium in THF or TMEDA at -45°C leads quantitatively to 102, as shown by the H-NMR spectrum. The assignment of the structure is made possible by comparison with the amino anaIog31. Both H- and l3C-NMR spectra of 102 are rather poorly diagnostic because they consist of broad signals. 

Bicyclobutanyllithium-TMED A 2 Phenyllithium-TMED A 2 H-C, chelated TMEDA... 

Intermediates 663 can be prepared by tin-lithium transmetallation with w-BuLi from a-stannylated vinyl sulfides974. Starting from l,l-bis(arylsulfanyl)ethenes, a reductive metallation with lithium naphthalenide at —70°C is a very efficient approach to lithiated vinyl sulfides975,976. Other methods involved bromine-lithium exchange977 or addition of methyl or phenyllithium to thioketenes978. A convenient method for the preparation of l-(methylsulfanyl) and l-(phenylsulfanyl) vinyllithiums was the treatment of 2-methoxyethyl sulfides with 2 equiv of w-BuLi-TMEDA at — 30 °C979. 

Given a dimeric structure of type 1, like that of phenyllithium (R = C6Hs) in the presence of tetramethylethylene diamine (TMEDA) [71], and a 1 1 mixture of deuterated and non-deuterated ligands R (d and h, respectively), the Li environments 2-4 exist ... 

Phenyllithium dissolves in hexane by addition of TMEDA. Hie phenyllithium TMEDA adduct subsequently crystallizes out of solution as the dimer (113) corresponding to general structural type (16)." With diethyl ether solvation, phenyllithium exists as a solid tetramer (114). In ether solution PhLi is known to be either dimeric or tetrameric. Monomeric phenyllithium was successfully crystallized with PMDETA as the ligand. This monomer is depicted as (115). Note the difference in the coordination number of the carbanionic center in the monomer (115), the dimer (113), and the tetramer (114), i.e. one, two and three, respectively. 

Wittig l56) and Waack 157) showed ebullioscopically and osmometrically, respectively, that phenyllithium is a dimer in etheral solvents. Thonnes and Weiss, 58) found a TMEDA complexed phenyllithium dimer in the solid state, and calculations performed by Schleyer et al. 159) similarly showed the dimer to be the most stable species. The 13C nmr spectrum of phenyl-6Li in THF shows a quintuplet at —118 °C which also reveals a dimeric aggregate l49,160). Thus experimental investigations of the structure in solution and in the solid state as well as a theoretical study (corresponding to the situation in the gas-phase) lead remarkably to the same result a phenyllithium dimer structure seems to be the most stable one. 

A similar dimeric structure has been established for the phenyllithium-TMEDA adduct (LiPh TMEDA)2 in which the p-phenyl ligands assume... 

Activation of organolithium compounds. n-Butyllithium and phenyllithium react very slowly with diphenylacetylene. However, the 1 1 complex of either lithium compound and TMEDA reacts with diphenylacetylene at room temperature. For example, the reaction of /-butyllithium under these conditions followed by carbonation gives cis-4,4-dimethyl-2,3-diphenyl-2-pentenoic acid (1) and a trace of 2-phenyl-3-f-butylindone (2). Thus addition takes place as well as metallation.1... 

The results reported here describe an investigation of the optimum conditions of preparation of the tertiary diamine phenyllithium, benzyl-lithium, allyllithium, and lithiated TMEDA complexes. These reagents were allowed to react with some common reagents to help delineate the synthetic usefulness of the complexes. 

In cases where the amount of TMEDA is to be minimized, the 2 1 ratio can be prepared at 60°C for five hours, but the reaction would have to be run slightly more dilute to maintain complete solubility. Another factor when preparing phenyllithium-TMEDA complexes with ratios... 

Laboratory quantities of the dark, red-brown solutions although highly reactive, were not pyrophoric when in air. More dilute solutions of the complexes were bright yellow. When phenyllithium-TMEDA solutions of higher ratios were prepared, the precipitated complexes were also bright yellow. The odor of phenol was noticed after hydrolysis of the air-oxidized complexes. 

Table III lists the decomposition rates of several organolithium-TMEDA complexes. The stability of the complexes is relatively good, but the presence of excess TMEDA above 1-mole equivalent significantly decreases stability. Solutions of the phenyllithium-TMEDA complex should be stored below 10 °C for long shelf life.

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... 

Phenyllithium-TMEDA in Benzene. Benzophenone. Added ben-zophenone dissolved in benzene at 5°C over 1 hr let warm 1 hr hydrolyzed, used extra benzene during work-up recrystallized from 1 1 methanol-ethanol mp 161 °C (lit. mp 162.5°C) 95%, triphenylcarbinol (36). 

Using the optimum conditions for benzene metalation as indicated by the carbonation studies, we found that other reactions typical of phenyllithium proceed in very high yield when phenyllithium-TMEDA is prepared this way. Some typical reactions are outlined below. 

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