The basicity gradient-driven migration of iodine: conferring regioflexibility on the substitution of fluoroarenes

Six different fluoroarenes were submitted to the same transformations. Direct deprotonation with alkyllithium or lithium dialkylamide as reagents and subsequent carboxylation afforded acids. These included 2,6-difluorobenzoic acid, 3,6-difluoro-2-iodobenzoic acid, 2-fluoro-6-iodobenzoic acid, 2-fluoro-3-iodobenzoic acid, 2,3-difluoro-4-iodobenzoic acid and 1-fluoro-2-naphthalenecarboxylic acid. If the aryllithium intermediate was trapped with iodine rather than with dry ice, an iodofluoroarene (2, 7, 12, 17, 19, and 24) was formed. Iodoarenes included 1,3-difluoro-2-iodobenzene, 1,4-difluoro-2,3-diiodobenzene, 1-fluoro-2,3-diiodobenzene, 2-fluoro-1,3-diiodobenzene, 2,3-difluoro-1,4-diiodobenzene, and 1-fluoro-2-iodonaphthalene. These, upon treatment with lithium diisopropylamide, underwent deprotonation and iodine migration. The resulting new aryllithium species was intercepted either by carboxylation, to give 2,6-difluoro-3-iodobenzoic acid, 2,5-difluoro-3,6-diiodobenzoic acid, 2-fluoro-3,6-diiodobenzoic acid, 2,3-difluoro-4,6-diiodobenzoic acid, and 1-fluoro-3-iodo-2-naphthalenecarboxylic acid, or by neutralization to produce the iodofluoroarenes which included 2,4-difluoro-1-iodobenzene, 1,4-difluoro-2,5-diiodobenzene, 2-fluoro-1,4-diiodobenzene, 1-fluoro-3-iodonaphthalene. The latter family of compds. was converted into another set of acids, which included 2,4-difluorobenzoic acid, 2,5-difluoro-4-iodobenzoic acid, 1-fluoro-3-naphthalenecarboxylic acid, by subsequent treatment with butyllithium or isopropylmagnesium chloride and carbon dioxide. [on SciFinder (R)]