76731-02-7Relevant articles and documents
Palladium(II)-Catalyzed Enantioselective Arylation of Unbiased Methylene C(sp3)?H Bonds Enabled by a 2-Pyridinylisopropyl Auxiliary and Chiral Phosphoric Acids
Yan, Sheng-Yi,Han, Ye-Qiang,Yao, Qi-Jun,Nie, Xing-Liang,Liu, Lei,Shi, Bing-Feng
, p. 9093 - 9097 (2018/07/25)
Enantioselective functionalizations of unbiased methylene C(sp3)?H bonds of linear systems by metal insertion are intrinsically challenging and remain a largely unsolved problem. Herein, we report a palladium(II)-catalyzed enantioselective arylation of unbiased methylene β-C(sp3)?H bonds enabled by the combination of a strongly coordinating bidentate PIP auxiliary with a monodentate chiral phosphoric acid (CPA). The synergistic effect between the PIP auxiliary and the non-C2-symmetric CPA is crucial for effective stereocontrol. A broad range of aliphatic carboxylic acids and aryl bromides can be used, providing β-arylated aliphatic carboxylic acid derivatives in high yields (up to 96 %) with good enantioselectivities (up to 95:5 e.r.). Notably, this reaction also represents the first palladium(II)-catalyzed enantioselective C?H activation with less reactive and cost-effective aryl bromides as the arylating reagents. Mechanistic studies suggest that a single CPA is involved in the stereodetermining C?H palladation step.
