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 1 are directly accessible by consecutive treatment with a suitable base and dry ice. In contrast, (2,6‐dichlorophenyl)‐ and (2,6‐bromophenyl)triethylsilane ( 2a and 2b ) were found to undergo deprotonation at the 5‐position (affording acids 3 and, after deprotection, 4 ), whereas the 1,3‐difluoro analog is known to react at the 4‐position. The 2,4‐dihalobenzoic acids 7 were selectively prepared from either the silanes 2 (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 8 (by base‐promoted migration of iodine to the 4‐position followed by iodine/magnesium permutation and subsequent carboxylation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)