Regioselective Metalation of Fluoroanilines. An Application to the Synthesis of Fluorinated Oxazolidinone Antibacterial Agents

Article abstract of DOI:10.1021/jo00121a050

The regioselective para lithiation of 3-fluoro- and 3,5-difluoroaniline stabase derivatives is described.These intermediates were subjected to a reaction sequence involving (1) transmetalation with zinc chloride, (2) a palladium-catalyzed coupling reaction with various pyridyl bromides, and (3) removal of the stabase protecting group, to generate fluorinated 4-(pyridyl)anilines.These compounds are key subunits for the synthesis of selected fluorinated oxazolidinone antibacterial agents.Representative applications of these intermediates to the synthesis of three potent oxazolidinone analogues are discussed.One facet of the described procedure involves a unique iodocyclocarbamation reaction featuring a pyridine additive.