Diastereoselective synthesis of chiral 3-substituted isoindolinones via rhodium( iii )-catalyzed oxidative C–H olefination/annulation

• Published in: Organic & biomolecular chemistry 2021-07, Vol.19 (26), p.5876-5887
• Main Authors: Li, Xue-Hong, Gong, Jun-Fang, Song, Mao-Ping
• Format: Article
• Language: English
• Subjects: Acrylic esters; Biological activity; Catalysis; Chemical reactions; Crystallography; Diastereoisomers; Esters; Organic chemistry; Rhodium; Stereoselectivity; Substitutes
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d1ob00656h

A new method for the direct and stereoselective synthesis of 3-substituted isoindolinones via Rh( iii )-catalyzed chiral N -sulfinyl amide directed asymmetric [4 + 1] annulation of benzamides with acrylic esters has been developed. The reaction proceeded through an oxidative C–H olefination and a subsequent cyclization by intramolecular aza-Michael addition, producing a series of diastereoisomeric chiral isoindolinones (20 examples) in generally good yields with a dr value up to 5.5 : 1. The absolute configurations of the newly formed C-stereocenters in the major and minor diastereomers of the catalysis product have been determined by X-ray crystal diffraction analysis to be S and R , respectively. The separation of the major diastereoisomers from the catalysis products and subsequent removal of the N -sulfinyl chiral auxiliary afforded enantiomerically pure ( S )-isoindolinones. The application of the obtained ( S )-isoindolinones in the synthesis of several biologically active isoindolinones such as ( S )-PD172938, ( S )-pazinaclone and ( S )-pagoclone is presented.