3- methoxybenzene-, lithium

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

Aromatic dibromides (1,2-dibromobenzene, 1,4-dibromobenzene, 1,2-dibromo-6-methoxybenzene, 2,7-dibromo-3,6-dimethoxynaphthalene, 5,10-dibromoanthracene) can be converted to lithioaryl bromides and subsequently to lithium bromoarenetellur-olates (Table 1 p. 155). An example of such a reaction sequence is given for 1,4-dibromobenzene3-4. With four moles of tert.-butyl lithium per mole of dibromoarene, the dilithio compounds that were formed were converted to the ditellurolates4 (Table 1 p. 155). 

However, neither copper(I) iodide nor photostimulation are absolutely necessary for the arylation of benzenetellurolate. Lithium benzenetellurolate and 1,2-bromoiodobenzene condensed in tetrahydrofuran at 20° to form 1,2-bis[phenyltelluro]benzene in 32% yield3. Sodium benzenetellurolate condensed similarly with l-chloro-2,4-dinitrobenzene at 20° in tetrahydrofuran/aqueous sodium hydroxide in the presence of a phase-transfer reagent. In this case 2,4-dinitrophenyl phenyl tellurium (m.p. 134°) was isolated in 30% yield4. Lithium methanetellurolate was arylated in tetrahydrofuran by iodobenzene5, 1,2-dibromobenzene, and l-bromo-2-methoxybenzene at 20°3. 

Reactions of methoxybenzenes or those bearing a fluoro substituent with lithium, an alkyllithium. or a bromo substituent with a Grignard reagent. 

Hunsdiecker Reactions. The Hunsdiecker reaction is the de-carboxylative halogenation of metal carhoxylate salts. The reaction of a,/3-unsaturated carboxylic acids with NCS and catalytic lithium acetate in acetonitrile-water provides the corresponding /3-halostyrenes in moderate yields under mild conditions. The reaction proceeds with a good degree of stereospecificity. For example, the reaction of 3-(4-methoxy-phenyl)-acrylic acid with NCS with a catalytic amount of lithium acetate at room temperature provides l-(2-chloro-vinyl)-4-methoxybenzene in good yield (eq 23). 3... 

When used in THF at room temperature, the base prepared from LiTMP and CoBr in a 3 1 ratio proves capable of deprotometalating different methoxybenzenes. The generated aryhnetal species can be trapped by different electrophiles iodine, anisaldehyde, and chlorodiphenylphosphine to respectively generate the corresponding iodide, alcohol, and phosphine in high yields and benzo-phenone, benzoyl chloride, and allyl bromide to afford the expected alcohol, ketone, and allylated compound in moderate yields (Table 27.10). The side formation of symmetrical dimers was observed in the course of these reactions, in particular using aUyl bromide such a side reaction (reduced by using the base in excess) could be initiated by one-electron transfer from a cobaltate species to the electrophile. This lithium-cobalt base is not suitable for the functionalization of sensitive substrates such as ethyl benzoate [109,110]. 

Another q>pToach to the aoidone skeleton, developed by Watanabe et al. 314), was based on an earlio- obsravation that small amounts of aoidones woe formed when benzynes were generated by diazotization of anthranilic acids 315-317). The acridones result in these cases from the reaction of benzynes with undiazotized anthranilic acids. Therefore, a new route was developed through tandem metallation synthesis. The lithium salt of methyl iV-methylanthranilate (250) could be easily coupled with the benzynes 251, 252, and 253, generated by treatment of chlorobenzene, 1 -bromo-2-methoxybenzene, and l-chloro-3,5-... 

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