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Palladium(II)‐Catalyzed Enantioselective Arylation of Unbiased Methylene C(sp 3 )−H Bonds Enabled by a 2‐Pyridinylisopropyl Auxiliary and Chiral Phosphoric Acids
Author(s) -
Yan ShengYi,
Han YeQiang,
Yao QiJun,
Nie XingLiang,
Liu Lei,
Shi BingFeng
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201804197
Subject(s) - enantioselective synthesis , chemistry , palladium , denticity , phosphoric acid , methylene , catalysis , aryl , combinatorial chemistry , reagent , medicinal chemistry , stereochemistry , organic chemistry , metal , alkyl
Enantioselective functionalizations of unbiased methylene C(sp 3 )−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(sp 3 )−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‐ C 2 ‐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.