Palladium-catalyzed alpha-arylation of esters

J Am Chem Soc. 2001 Aug 22;123(33):7996-8002. doi: 10.1021/ja010797+.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Bromides / chemistry
  • Catalysis
  • Esters / chemistry*
  • Flurbiprofen / analogs & derivatives
  • Flurbiprofen / chemical synthesis*
  • Flurbiprofen / chemistry*
  • Lithium / chemistry
  • Molecular Structure
  • Naproxen / analogs & derivatives
  • Naproxen / chemical synthesis*
  • Naproxen / chemistry*
  • Organosilicon Compounds / chemistry
  • Palladium / chemistry
  • Phosphines / chemistry

Substances

  • Acetates
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bromides
  • Esters
  • Organosilicon Compounds
  • Phosphines
  • nitroflurbiprofen
  • butyl acetate
  • Naproxen
  • Flurbiprofen
  • Palladium
  • Lithium
  • hexamethylsilazane