Alcohols, lateral lithiation

Methylbenzyl alcohol 529 can just about be lithiated by treatment with BuLi in EtiO at room temperature, but the activation of the methyl group is very weak. Lateral lithiation of cresol 530 is even harder to achieve, and the superbase conditions required... 

The latter has been synthesised from 3,5-dimethoxy benzyl alcohol by lithiation route Thus, lithiation of 3,5-dimethoxy benzyl alcohol (using n-BuLi in presence of TMEDA) followed by reaction with excess of CO and later treatment with acid gives 79. 

Knight explored the C2-lithiation of indole-3-carboxylic acids [326, 327]. Similar to the reaction with alcohol 100, two equivalents of LDA were used to generate dianion intermediates which upon quenching with electrophiles gave 2-(substituted)indole-3-carboxylic acids. This strategy was later used by Fisher... 

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