Diastereoselective synthesis of chiral 3-substituted isoindolinones via rhodium(iii)-catalyzed oxidative C–H olefination/annulation. Issue 26 (14th June 2021)

• Record Type: Journal Article
• Authors: Li, Xue-Hong; Gong, Jun-Fang; Song, Mao-Ping
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 26(2021)
• Page Start: 5876
• Page End: 5887
• Publication Date: 2021-06-14
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00656h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A new method for the direct and stereoselective synthesis of chiral 3-substituted isoindolinones has been developed. Separation of the diastereoisomers and further transformations provide some important chiral isoindolinones. Abstract : 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.