3- methyl benzene-, lithium

When treated with lithium diisopropylamide, the unsubstituted simple bicyclic y-lactam, hexa-hydro-3//-pyrrolizin-3-one (1), furnishes the corresponding enolate which reacts with (halo-methyl)benzenes to give the a-alkylation products with rather poor diastereoselectivity10. The major product 2 has cis configuration. Equilibration of the product with base gives a 72 28 mixture in favor of the frans-diastereomer10. 

Dimethylamino)methyl]-5-methylphenyl]lithium is a white crystalline solid and is pyrophoric in air. Furthermore, it is soluble in hydrocarbons and ethers. Molecular weight determinations in benzene have established a tetrameric structure.12 In THF, like [2-[(dimethylamino)-methyl]phenyl]lithium, this tetramer breaks down to a dimeric species. 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

The active center a-methyl(styryl)lithium undergoes a slow decomposition in benzene at 30 °C. Using ethyllithium as the initiator, Margerison and Nyss demonstrated 289) that the main products of this decomposition process are lithium hydride and l,3-dimethyl-3-phenyl-l-propylindane. Their reaction sequence follows ... 

Tetrakis(pyridine)iron(II) chloride (0.500 g, 1.13 mmol, 1.00 equiv.) is suspended in tetrahydrofuran (3.0 mL) at 23 °C. In a separate vial, 2-[(dimethylamino)methyl]phenyl-lithium (0.319 g, 2.26 mmol, 2.00 equiv.), is dissolved in tetrahydrofuran (2.5 mL) at 23 C. Both vials are cooled to -40 °C and the solution of 2-[(dimethylamino)methyl]-phenyllithium is added dropwise to tetrakis(pyridine)iron(lI) chloride. The reaction mixture is stirred at -40 C for 30 min and then warmed to 23 C and stirred for 2 h. The solvent is removed in vacuo, benzene (15 mL) is added, and the dark purple mixture is filtered through a pad of Celite, eluting with benzene. The solvent is removed in vacuo to afford bis[2-(A, A -dimethylaminomethyl)-phenyl-C,N]pyridineiron(II) 0.365 g (80%). 

The equihbrium shown in equation 3 normally ties far to the left. Usually the water formed is removed by azeotropic distillation with excess alcohol or a suitable azeotroping solvent such as benzene, toluene, or various petroleum distillate fractions. The procedure used depends on the specific ester desired. Preparation of methyl borate and ethyl borate is compHcated by the formation of low boiling azeotropes (Table 1) which are the lowest boiling constituents in these systems. Consequently, the ester—alcohol azeotrope must be prepared and then separated in another step. Some of the methods that have been used to separate methyl borate from the azeotrope are extraction with sulfuric acid and distillation of the enriched phase (18), treatment with calcium chloride or lithium chloride (19,20), washing with a hydrocarbon and distillation (21), fractional distillation at 709 kPa (7 atmospheres) (22), and addition of a third component that will form a low boiling methanol azeotrope (23). 

Alternatively, 25.0 g of either 3j3,5a-dihydroxy-17a-methyl-17j3-carbomethoxyandrostan-6-one (Ilia) or 25.0 g of its 3)3-acetate (Hlb), are dissolved in dry tetrahydrofuran (1,250 ml, freshly distilled over lithium aluminum hydride) and dry benzene (2,000 ml) is added. Methyl magnesium bromide in ether solution (3 M, 750 ml) is added to the stirred solution and the resulting mixture is stirred at room temperature for 16 hours. An additional quantity of methyl magnesium bromide solution in ether (2M, 375 ml) is added, and 1,250 ml of the solvent mixture are distilled off. The resulting mixture is refluxed for 5 hours and worked up as described above, yielding compound (V) as a colorless oil. 

In one case, the addition of lithiated 1,3-dithiane to ( )-l-nitropropene gave an adduct in modest enantiomeric excess (43% ee). In an independent study chiral lithium [(S)-(l-(dimethylamino)-ethyl](methyl)phenylcupratc and lithium mcthoxy(methyl)eupratc were reacted with ( )-(2-ni-troethenyl)benzene to give adducts in 1-2% enantiomeric excess36. 

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°. 

Thiophenol, lithium salt [Benzenethiol, lithium salt], 55, 122 Toluene, 4-bromo- [Benzene, 1 bromo 4 methyl-], 55, 49... 

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. 

Polarization is found in reactions involving chlorides. 1,1-Dichloro-2,2-dimethylcyclopropane (26) reacts with lithium ethyl in benzene-ether solution (40°) giving mainly l-chloro-2,2-dimethylcyclopropane (27 X = H) and 3-methyl-l,2-butadiene (28) both of which are polarized (Ward et al., 1968). If n- or t-butyl lithium are used in the reaction, the butene produced by disproportionation shows only net polarization. 

Therefore, another analogous reaction was studied with a more reactive olefin, viz. methyl acrylate, which reacts with (+)-methylneophylphenyltin deuteride (86) at room temperature and yields after 18 h again an optically inactive adduct which is reduced with lithium aluminum hydride to give racemic isotopically labeled (55) 44). After 18h in the presence of AIBN at room temperature, (86) only loses 30% of its optical activity in benzene. The fact that the obtained adduct is optically inactive might be due to the nucleophilicity of methyl acrylate, which might be important enough to cause the racemization of (56). 

In preparation of di-//-mcthylcncbis(incthyl-pcntamcthylcyclopcntadicnvl)dirhod-ium complexes by aerobic oxidation of a solution of the halocomplex and methyl-lithium or trimethylaluminium in ether-benzene, the reaction mixture occasionally ignited and burned violently. Full precautions and a working scale below 1 mmol are recommended. 

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