Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct

• Published in: Angewandte Chemie International Edition (ISSN: 1433-7851), vol. 55, num. 17, p. 5282-5285
• Weinheim: Wiley-Blackwell, 2016

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 fourcenter 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.

Keywords: asymmetric synthesis ; kinetic resolution ; multicomponent reactions ; organocatalysis ; reaction mechanisms

Reference

• EPFL-ARTICLE-218177
• doi:10.1002/anie.201600751
• View record in Web of Science

Record created on 2016-04-22, modified on 2017-05-12