title: Palladium-catalyzed alpha-arylation of esters.
abstract: 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 degrees C with very good yields and high selectivities for monoarylation. Important nonsteroidal antiinflammatory 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Moradi
authors.forename: S L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D000085:Acetates / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry; D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D009288:Naproxen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D017646:Organosilicon Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry
chemical_list: D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001965:Bromides; D004952:Esters; D017646:Organosilicon Compounds; D010720:Phosphines; C095631:nitroflurbiprofen; C006848:butyl acetate; D009288:Naproxen; D005480:Flurbiprofen; D010165:Palladium; D008094:Lithium; C024548:hexamethylsilazane