Reversed-Polarity Synthesis of Diaryl Ketones through Palladium-Catalyzed Direct Arylation of 2-Aryl-1,3-dithianes

Yücel B., Walsh P. J.

ADVANCED SYNTHESIS & CATALYSIS, vol.356, no.17, pp.3659-3667, 2014 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 356 Issue: 17
  • Publication Date: 2014
  • Doi Number: 10.1002/adsc.201400695
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3659-3667
  • Istanbul Technical University Affiliated: Yes


An umpolung approach to the synthesis of diaryl ketones has been developed based on in situ generation of acyl anion equivalents and their catalytic arylation. This method entails the base-promoted, palladium-catalyzed direct C-H arylation of 2-aryl-1,3-dithianes with aryl bromides. Use of MN(SiMe3)2 (M=Li, Na) base results in reversible deprotonation of the weakly acidic dithiane. In the presence of a Pd(NiXantphos)-based catalyst and aryl bromide, cross-coupling of the metallated 2-aryl-1,3-dithiane takes place under mild conditions (2 h at rt) with yields as high as 96%. The resulting 2,2-diaryl-1,3-dithianes were converted into diaryl ketones by either molecular iodine, N-bromo succinimide (NBS) or Selectfluor in the presence of water. The dithiane arylation/hydrolysis can be performed in a one-pot procedure to yield a variety of diaryl ketones in good to excellent yields. This method is suitable for rapid and large-scale synthesis of diaryl ketones. A one-pot preparation of anti-cholesterol drug fenofibrate (TriCor (R)) has been achieved on 10.0 mmol scale in 86% yield.