Metalation/functionalization sequences applied to 2-bromo-3-fluoroquinolines

Mono- and disubstituted 2-bromo-3-fluoroquinolines are readily accessible. They can be converted into the 3-fluoroquinoline-2-carboxylic acids by consecutive halogen/metal permutation and into the 2-bromo-3-fluoroquinoline-4-carboxylic acids by consecutive deprotonation and carboxylation. The latter compounds can be reduced to afford the 3-fluoroquinoline-4-carboxylic acids . The yields are excellent throughout. Rather than to introduce one functional group alternatively at the 2- or 4-position, one may also attach two different functional groups sequentially to both sites.