Quaternary Chiral Phthalides Enabled by Dirhodium(II)/Phosphine Catalyzed Asymmetric Carbonyl Addition Cascade

Abstract

The catalytic asymmetric synthesis of chiral phthalides has garnered considerable interest. However, the construction of phthalides with a chiral quaternary carbon stereocenter still remains challenging. In this study, we developed a new strategy toward catalytic asymmetric synthesis of chiral 3,3disubstituted phthalides via a dirhodium(II)/phosphine-catalyzed carbonyl addition cascade, yielding phthalides with up to 97% ee values. The reaction proceeded through dirhodium(II)/phosphine-catalyzed asymmetric carbonyl addition of arylboronic acids to isoquinoline-1,3,4(2H)-triones, followed by base-mediated ring contraction.