Phenols Methyllithium

One 1-ml aliquot is added to 1.0 ml of freshly-distilled 1,2-dibromo-ethane (bp 132°C) in an oven-dried flask which contains a static atmosphere of nitrogen or argon. After the resulting solution has been allowed to stand at 25°C for 5 min, it Is diluted with 10 rat of water and titrated for base content (residual base) to a phenolphthalein endpoint with standard 0.100 M hydrochloric acid. The second 1-mL aliquot is added cautiously to 10 ml of water and then titrated for base content (total base) to a phenol phthalein endpoint with standard aqueous 0.100 M hydrochloric acid. The methyllithium concentration is the difference between the total base and residual base concentrations.2 Alternatively, the methynithiura concentration may be determined by titration with a standard solution of sec-butyl alcohol employing 2,2 -bipyridyl as an indicator. 

Fig (14) Olefin (107) has been converted to cyclic ether (114) by standard reactions. Its transformation to enone (115) is accomplished by annelation with methyl vinyl ketone and heating the resulting diketone with sodium hydride in dimethoxyethane. The ketoester (116) is subjected to Grignard reaction with methyllithium, aromatization and methylation to obtain the cyclic ether (117). Its transformation to phenolic ester (119) has been achieved by reduction, oxidation and esterification and deoxygenation. 

Alkynes and trimethylsilylethyne also react with phenol in the presence of SnCLj-BU3N reagent to give a-alkylvinyl and /3-silylvinyl derivatives, respectively (Eqs 92, 93). In the latter case methyllithium treatment gives /3-monostannylated derivative. 

Fig. (16). The alcohol (171) was converted to the keto ether (185) applying the standard organic reactions and this on subjection to Robinson annelation. The resulting adduct on treatment with sodium methoxide in methanol afforded the tricyclic ketone (187) which is converted to another keto ether (188). It is converted to tertiary alcohol (189) by treatment with methyllithium. Acid treatment of the alcohol produced the phenol (190). Its methyl derivative (191) is converted to pisiferol (192) by treatment with zinc and zinc iodide. Its methyl derivative (193) was converted to ester (195) via oxidation, reduction, tosylation and detosylation. The reagents mentioned accomplished its conversion to pisiferic acid (196).

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