title: Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct.
abstract: Reaction of isonitriles with 3-(arylamino)isobenzofuran-1(3H)-ones in the presence of a catalytic amount of an octahydro (R)-binol-derived chiral phosphoric acid afforded 3-oxo-2-arylisoindoline-1-carboxamides in high yields with good to high enantioselectivities. An enantioselective Ugi four-center three-component reaction of 2-formylbenzoic acids, anilines, and isonitriles was subsequently developed for the synthesis of the same heterocycle. Mechanistic studies indicate that the enantioselectivity results from the dynamic kinetic resolution of the primary Ugi adduct, rather than from the C-C bond-forming process. The resulting heterocycle products are of significant medicinal importance.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Ao
authors.affiliation: Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Zhi-Tang
authors.initials: ZT
authors.lastname: Huang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China. dxwang@iccas.ac.cn.
authors.forename: De-Xian
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Key Laboratory of Bioorganic Phosphorous and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100184, China. wangmx@tsinghua.edu.cn.
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015, Lausanne, Switzerland. jieping.zhu@epfl.ch.
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
keywords: asymmetric synthesis; kinetic resolution; multicomponent reaction; organocatalysis; reaction mechanisms