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

摘要

A new method for the direct and stereoselective synthesis of 3-substituted isoindolinones via Rh(Ⅲ)-cata-lyzed 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 cycliza-tion 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.