Premium
Reversed‐Polarity Synthesis of Diaryl Ketones through Palladium‐Catalyzed Direct Arylation of 2‐Aryl‐1,3‐dithianes
Author(s) -
Yucel Baris,
Walsh Patrick J.
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400695
Subject(s) - chemistry , aryl , catalysis , palladium , dithiane , deprotonation , organic chemistry , bromide , yield (engineering) , umpolung , one pot synthesis , medicinal chemistry , combinatorial chemistry , nucleophile , alkyl , ion , materials science , metallurgy
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(SiMe 3 ) 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.