Réactions d'ortho lithiation de composés benzéniques et hétéroaromatiques-π-excédentaires dirigées par la fonction acide carboxylique

Abstract

This review surveys and classifies the lithiations of aromatic and π-excessive heteroaromatic systems directed by the carboxylic acid group. Treatment of a benzoic acid with 2.2 equivalents of the 1:1 complex sec-butyllithium·tetramethylethylene diamine in THF at −90°C gives an ortho metallated species stable at low temperatures (−78°C) which may be quenched with various electrophiles. These reactions are capable of producing novel functionalities ortho to the carboxylic acid group and do not require protection-deprotection techniques. In contrast with a few exceptions, lithiation of meta-substituted benzoic acids permits the regioselective preparation of 2,3-disubstituted derivatives. Alternatively, 2,3-disubstituted benzoic acids are readily available by lithiating 1,2-disubstituted compounds, metallation occurring ortho to the more effective directing group. In turn the 2,3-disubstituted benzoic acids can be utilized to prepare 2,3,4- or 2,3,6-trisubstituted benzoic acids, etc. Lithiations in the position ortho to the carboxylic acid group have also been reported on heteroatomic systems. Thiophens and furans substituted by a carboxylic acid group may be lithiated and the site of metallation depends on the nature of the deprotonating agent.