Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds.

We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives. The method employs a carboxylic acid 2-methylthioaniline- or 8-aminoquinoline amide substrate, aryl or alkyl iodide coupling partner, palladium acetate catalyst, and an inorganic base. By employing 2-methylthioaniline auxiliary, selective monoarylation of primary sp(3) C-H bonds can be achieved. If arylation of secondary sp(3) C-H bonds is desired, 8-aminoquinoline auxiliary may be used. For alkylation of sp(3) and sp(2) C-H bonds, 8-aminoquinoline auxiliary affords the best results. Some functional group tolerance is observed and amino- and hydroxy-acid derivatives can be functionalized. Preliminary mechanistic studies have been performed. A palladacycle intermediate has been isolated, characterized by X-ray crystallography, and its reactions have been studied.