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B(C 6 F 5 ) 3 /Chiral Phosphoric Acid Catalyzed Ketimine–Ene Reaction of 2‐Aryl‐3 H ‐indol‐3‐ones and α‐Methylstyrenes
Author(s) -
Zhang QingXia,
Li Yao,
Wang Jie,
Yang Chen,
Liu ChengJun,
Li Xin,
Cheng JinPei
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915226
Subject(s) - phosphoric acid , enantioselective synthesis , chemistry , catalysis , ene reaction , aryl , reactivity (psychology) , stereoselectivity , insertion reaction , hydrogen bond , medicinal chemistry , stereochemistry , organic chemistry , molecule , medicine , alkyl , alternative medicine , pathology
The enantioselective ketimine–ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine–ene reactions of 2‐aryl‐3 H ‐indol‐3‐ones with α‐methylstyrenes were achieved by utilizing a B(C 6 F 5 ) 3 /chiral phosphoric acid (CPA) catalyst. These ketimine–ene reactions proceed well with low catalyst loading (B(C 6 F 5 ) 3 /CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2‐allyl‐indolin‐3‐ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee ). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C 6 F 5 ) 3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen‐bonding interactions, especially the enhanced N−H⋅⋅⋅O hydrogen‐bonding interaction, differentiates the free energy of the transition states of CPA and B(C 6 F 5 ) 3 /CPA, thereby inducing the improvement of stereoselectivity.