Reversed-polarity synthesis of Diaryl Ketones through palladium-catalyzed direct Arylation of 2-Aryl-1,3-dithianes

Baris Yucel*, Patrick J. Walsh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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 MNACHTUNGTRENUNG( 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) has been achieved on 10.0 mmol scale in 86% yield.

Original languageEnglish
Pages (from-to)3659-3667
Number of pages9
JournalAdvanced Synthesis and Catalysis
Volume356
Issue number17
DOIs
Publication statusPublished - 24 Nov 2014

Funding

FundersFunder number
National Institute of General Medical SciencesNIGMS 104349

    Keywords

    • C-C bond formation
    • Cross-coupling
    • Dithianes
    • Ketones
    • Palladium
    • Umpolung

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