Methyl lithium determination

IQ. To determine the concentration of chloride ion, - a 5-mL aliquot of the methyl lithium solution is cautiously added to 25 ml of water and the resulting solution is acidified with concentrated sulfuric acid and then treated with 2-3 ml of ferric ammonium sulfate [Fe(NH4)( 04)2 12 H2O] indicator solution and 2-3 ml of benzyl alcohol. The resulting mixture is treated with 10.0 mL of standard aqueous 0.100 M silver nitrate solution and then titrated with standard aqueous 0.100 H potassium thiocyanate solution to a brownish-red endpoint. 

Upon hydrogenation of 24 a 1,2-rearrangement of the epoxide occurred generating aldehyde 25 as a mixture of diastereoisomers. After reaction with methyl lithium, the diastereomeric alcohols 26 and 27 were separated and isolated in yields of 23% and 71%. While alcohol 26 as the minor diastereo-isomer could be oxidized with pyridinium dichromate (PDC) and methyle-nated to give the enantiomer of kelsoene (cnM), its diastereoisomer 27 with the inverse configuration at C-7 required a supplementary epimerization step with sodium methanolate. The enantiomerically pure ent- allowed for the determination of the absolute configuration of natural kelsoene (1) [9, 10]. The previously reported assignment based on NMR-correlation experiments [5] was corrected. 

The enantiomeric excess of the lactones can be determined either via conversion with methyl-lithium to the corresponding a,a-dimethyldimethanol derivatives and H-NMR spectroscopy in the presence of chiral shift reagents169 or directly by capillary GC on cyclodextrin columns170a. 

Cyclohexadienol was prepared by Rickborn in 1970 from reaction of the epoxide of 1,4-cyclohexadiene with methyl lithium.100 A hydrate of naphthalene, 1-hydroxy-1,2-dihydro-naphthalene was prepared by Bamberger in 1895 by allylic bromination of O-acylated tetralol (1-hydroxy-l,2,3,4-tetrahydronaphthalene) followed by reaction with base.101 Hydrates of naphthalene and other polycylic aromatics are also available from oxidative fermentation of dihydroaromatic molecules, which occurs particularly efficiently with a mutant strain (UV4) of Pseudomonas putida.102,103 The hydrates are alcohols and they undergo acid-catalyzed dehydration to form the aromatic molecule by the same mechanism as other alcohols, except that the thermodynamic driving force provided by the aromatic product makes deprotonation of the carbocation (arenonium ion) a fast reaction, so that in contrast to simple alcohols, formation of the carbocation is rate-determining (Scheme 6).104,105... 

The NMR spectra of organolithium derivatives have received considerable attention. At — 60°C, the Li NMR spectrum of 57% C-enriched methyllithium shows a pattern due to lithium-carbon coupling which can only readily be explained in terms of a tetramer [LiMe]4 with three methyl groups attached to each lithium. The chemical shift of the methyl group determined by INDOR is —16 ppm in tetrahydrofuran. It was concluded that the shift is due to 0.1 electrons on each methyl group and the bond is predominantly covalent (151,152). A similar result is found for [(Mea C)Li]4 and — Li) was... 

Continuing their investigation of the stereochemistry of tervalent phosphorus, Mikolajczyk and his co-worker have shown that optically active O-methyl ethyl-phenylphosphinite (112) and S -ethyl ethylphenylthiophosphinite (113) react with methyl-lithium and sodium methoxide with predominant inversion of configuration at phosphorus. The absolute configuration of (113) was established by conversion into ethylmethylphenylphosphine sulphide, and the stereochemical course of the nucleophilic displacements was determined by conversion of the initial products into the corresponding oxide and sulphides, as shown in Scheme 9. 

Further evidence for the tetrahedral structure and the local environment hypothesis is provided by the determination of the 13C-7Li couplings of methyl lithium enriched by 13C140). The local environment hypothesis predicts seven lines, as observed, whereas nine lines would appear had the infra-molecular exchange been fast. 

Continuation of these studies allowed Brown to determine the heat of activation, AH, and the entropy of activation, AS of the dissociation of the tetrameric methyl lithium in diethyl ether and the tetrameric r-butyl lithium in cyclopentane1455, namely,... 

Carbanions can also function as electron-donors to organoboron compounds the products are complex ions. Thus reaction of trimethylboron with methyl-lithium in ethereal solution affords lithium tetramethylborate. The aromatic analog, sodium tetraphenylborate Na[B(C6H5)4], is an important reagent for gravimetric determination of potassium and a number of other ions, because lithium and sodium tetraphenylborate are soluble in water whereas the potassium, rubidium, cesium, and ammonium salts are almost completely insoluble therein. 

Table 6.15 shows relative rate constants reported for the addition of methyl-lithium to benzophenone derivatives having the general structure 112 in diethyl ether solution at 0°C. Determine the Hammett p for this reaction. Is the value of p consistent with your expectation for nucleophilic addition of methyllithium to the carbonyl group ... 

In an attempt to perform an addition of an allyl anion to a reactive alkene, syn-1-allyloxynorbornene was treated with methyl-lithium. After hydrolysis (413) and (414) were obtained in the ratio 3 7. It is concluded that (413) does not arise by a concerted [2 + 4] cycloaddition of (410) followed by cleavage of the initial alkoxy carbanion (41IX but rather a stepwise process via (412) leads to the two products. Treatment of cycloheptatriene with potassium amide gives dimers (417) (70%) and (418) (14%). To determine whether the reaction involves addition of cycloheptatriene to cycloheptatrienyl anion (415) or to the adduct ion (416) the experiment was performed with 1,2,3,4,5,6-hexadeuteriocycloheptatriene. The isotope distri-... 

An alternative interpretation of these fractional kinetic orders in alkyl-lithium concentration as proposed by Wakefield [19] is that the rate-determining step involves coordination of a DPE molecule to one face of the polyhedral organolithium aggregate. As suggested previously [8], incomplete or stepwise dissociation equilibria such as those shown in Scheme 3 would be expected to require less energy as predicted by theoretical calculations [32]. It is important to note that Brown and coworkers [34, 35] have reported that dissociation energies for tetramer-dimer equilibria are 46.1 kj/mol and lOOkJ/mol for methyl-lithium in ether [34] and ferf-butyllithium in cyclopentane [35], respectively. 

The lithium-(-)-sparteine complex, generated by deprotonation of 1-methylindene, does not lose its configuration in diethyl ether solution even at room temperature80 presumably, the observed major diastcreonier is the thermodynamically determined product. Substitution with carbonyl compounds leads to 1-substituted (fl)-l-methyl-l//-indenes with >95% ee in high yields81. 

To a solution of 5 mmol of 1,3-diphcnyl 3-[(S )-2-mcthoxymethyl-l-pyrrolidinyl]-2-propenyl[lithium in 10 mL of tort-butyl methyl ether (prepared according to Section D. 1.1.1.2.2.3.) at 0°C. 6.25 mmol of the aldehyde (and eventually 6.25 mmol of lithium halogenide in 27 mL of leri-butyl methyl ether) are added dropwise. Stirring is continued for 2 h and 0.39 g (5.0 mmol) of acetyl chloride are added. After 2 h stirring at r.t., 10 mL of the solvent, 50 mL of diethyl ether and 10 mL of 2 N aq hydrochloric acid are added and stirring is continued for 2 h at 20 C. The organic layer is extracted with three 20 mL-portions of water and the aqueous solutions are reextracted with diethyl ether. The combined aqueous solutions are dried over Na,S04, concentrated in vacuum and the residue distilled to yield a mixture of xyn- and on/i-ketones >90% ee, determined by H-NMR with Pr(hfc)3. 

Conjugate Addition. To a solution of 1.5 mmol of lithium dialkylcuprate at — 25 CC is added 1 mmol of methyl ( )-3-[(25,45,55)-3-benzyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinyl]-propenoate dissolved in 1 mL of dry diethyl ether. After 30 ntin at — 25 C, the mixture is treated with an aq NH3/NH4C1 pH 8 buffer solution and then stirred at r.t. for 15 min. After diethyl ether extraction, the organic layers are dried over Na,S()4 and filtered and the solvent is evaporated under reduced pressure. The crude products are checked by H- and l3C-NMR analyses in order to determine the diastereomer ratios (g 95 5) and then purified by flash chromatography (hexane/ethyl acetate 80 20) yield 70-72%. 

The exact time and temperature required for complete reaction must be determined for each individual compound. It has been observed that nucleophilic demethylation of methyl o-alkoxyaryl ethers is accelerated relative to anisole [Benzene, methoxy-],6 and this reaction is no exception. Lithium diphenylphosphide cleavage of anisole is complete in about 4 hours in refluxing tetrahydrofuran, whereas the present reaction is complete within 2 hours at 25°. 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

Synthesis of comb (regular graft) copolymers having a PDMS backbone and polyethylene oxide) teeth was reported 344). These copolymers were obtained by the reaction of poly(hydrogen,methyl)siloxane and monohydroxy-terminated polyethylene oxide) in benzene or toluene solution using triethylamine as catalyst. All the polymers obtained were reported to be liquids at room temperature. The copolymers were then thermally crosslinked at 150 °C. Conductivities of the lithium salts of the copolymers and the networks were determined. 

Glycosyl-linkages were determined by GC-EIMS of the partially methylated alditol acetates. RG-II samples (2 mg) were methylated using sodium methyl sulfmyl carbanion and methyl iodide in dimethyl sulfoxide [24] followed by reduction of the uronosyl groups with lithium triethylborodeuteride (Superdeuteride , Aldrich) [23,25]. Methylated and carboxyl-reduced samples were then submitted to acid hydrolysis, NaBIlt reduction and acetylation, partially methylated alditol acetates being analysed by EIMS on two fused-silica capillary columns (DB-1 and DB-225) [20]. 

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