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

Article abstract of DOI:10.1007/BF00817261

The reaction of benzyl bromide with bis-(N- and C-ortho)-lithiated chloroanilides 4, 5, and 6 has been examined.It has been found that in the case where the lithiated compound was derived from meta-methoxyanilides, pre-addition of LiBr or TMEDA 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 or TMEDA complex in which the C-lithium bond appears to be more accessible towards electrophiles.The practical synthesis of o-benzylchlorobenzoic acids 10, 11, and 12 was accomplished via ionic reductive cleavage (Et3SiH/TiCl4) of the corresponding phthalides 18, 19, and 20.The acids 10, 11b, and 11c afforded the corresponding anthrones, upon treatment with trifluoroacetic anhydride which were oxidized by chromium trioxide to the new chloroantraquinones 21, 22, and 23. - Keywords: Chlorophthalides; Reduction; Benzylation; Benzylbenzoic acids; Chloroantraquinones