Buttressing effects rerouting the deprotonation and functionalization of 1,3-dichloro- and 1,3-dibromobenzene

A systematic comparison between 1,3-difluorobenzene, 1,3-dichlorobenzene, and 1,3-dibromobenzene did not reveal major differences in their behavior towards strong bases such as lithium diisopropylamide or lithium 2,2,6,6-tetramethylpiperidide. Thus, all 2,6-dihalobenzoic acids are directly accessible by consecutive treatment with a suitable base and dry ice. In contrast, (2,6-dichlorophenyl)- and (2,6-bromophenyl)triethylsilane undergo deprotonation at the 5-position (affording the 4-carboxy derivs. and the 3,5-dihalobenzoic acids after deprotection), whereas the 1,3-difluoro analog is known to react at the 4-position. The 2,4-dihalobenzoic acids were selectively prepd. from either the silanes by bromination at the 4-position, metalation and carboxylation of the neighboring position, followed by desilylation and debromination or the 1,3-dihalo-2-iodobenzenes by base-promoted migration of iodine to the 4-position followed by iodine/magnesium permutation and subsequent carboxylation. [on SciFinder (R)]