Palladium-Catalyzed Ortho Alkoxylation of Oxazoline\nDerivatives: An Avenue to Reach Meta-Substituted Electron-Rich Arenes\nExploiting Oxazoline as a Removeable Directing Group

An efficient and\nhighly regioselective palladium-catalyzed oxazoline-directed\nalkoxylation is reported. The reaction proceeds under air and mild\ntemperatures (60 °C). A series of alcohols can be used as alkoxylating\nagents and concomitantly act as reaction solvents, whereas primary\nand secondary alcohols are tolerated. Furthermore, fluorinated alcohols\ncan be applied as well, introducing pharmaceutically relevant fluorine-containing\ngroups. 1,3-Dialkoxylated products can be further subjected to hydrolysis\ntransforming the oxazoline-directing group to a carboxylic acid, which\ncan be removed by decarboxylation if desired. This approach demonstrates\nthe capability to reverse the conventional site selectivity of electrophilic\naromatic substitution reactions, since it allows the synthesis of\narenes with two electron-donating groups in a 1,3-relationship.