A new and simple one-pot procedure for the palladium-catalyzed intermolecular alpha-arylation of esters is described. A number of esters can be functionalized with a wide range of aryl bromides using Pd(OAc)(2) or Pd-2(dba)(3) and bulky electron-rich o-biphenyl phosphines 1-3. Under the reaction conditions, using LiHMDS as base, alpha-arylation proceeds at room temperature or at 80 degreesC with very good yields and high selectivities for monoarylation. Important nonsteroidal anti inflammatory drug derivatives such as (+/-)-naproxen tert-butyl ester and (+/-)-flurbiprofen tert-butyl ester can be prepared in 79%, and 86% yield, respectively. The catalyst system based on the di-tert-butylphosphine (2) is also active for the alpha-arylation of esters using aryl chlorides. Furthermore, using (3) the alpha -arylation of trisubstituted ester enolates can be accomplished to provide compounds that have quaternary centers.
“Palladium-Catalyzed α-Arylation of Esters”, J. Am. Chem. Soc., 2001, 123(33), 7996-8002.