Catalytic Asymmetric <i>De Novo</i> Synthesis of Chiral Pyrroles Through Desymmetrizing Oxidative [3+2]‐Cycloaddition and the Van Leusen Reaction

Central chirality in heteroarene derivatives arising from unsymmetrically substituted heteroarene rings is an intriguing but underexplored topic. Herein, we reported the first catalytic enantioselective de novo construction of centrally chiral pyrroles through desymmetrizing oxidative [3+2]-cycloaddition by employing silver catalysis. This judicious desymmetrization can produce at least four continuous stereogenic centers without creating any additional stereocenter. Furthermore, to introduce a more diverse set of substituents, we developed the first catalytic asymmetric Van Leusen reaction with α-substituted TosMIC for the synthesis of centrally chiral pyrroles. A wide range of polycyclic 2-substituted, 3,4-fused pyrroles were obtained in high yields and with good to high enantioselectivities. This report includes the elaboration of methanobenzo[f]isoindole to synthetically challenging building block chiral isoindole compounds, which are synthesized enantioselectively for the first time.