Application of organolithium and related reagents in synthesis XVI: Synthetic strategies based on aromatic metallation. A concise regiospecific conversion of chlorobenzoic acids into their benzylated derivatives

Abstract

The reaction of benzyl bromide withbis-(N- and C-ortho)-lithiated chloroanilides4,5, and6 has been examined. It has been found that in the case where the lithiated compound was derived frommeta-methoxyanilides, pre-addition of LiBr orTMEDA was required to achieve C-benzylation. These results were accounted for by the conversion of the usually formed dimer into a mixed dimer with the LiBr orTMEDA complex in which the C-lithium bond appears to be more accessible towards electrophiles. The practical synthesis of σ-benzylchlorobenzoic acids10,11, and12 was accomplishedvia ionic reductive cleavage (Et3SiH/TiCl4) of the corresponding phthalides18,19, and20. The acids10,11b, and11c afforded the corresponding anthrones, upon treatment with trifluoroacetic anhydride which were oxidized by chromium trioxide to the new chloroantraquinones21,22, and23.