Cobalt-Catalyzed Enantioselective C-H Carbonylation towards Chiral Isoindolinones

Transition metal-catalyzed enantioselective C-H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed an unprecedented enantioselective C-H carbonylation catalyzed by inexpensive and readily available cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, and parallel kinetic resolution, affording a broad range of chiral isoindolinones in good yields with excellent enantioselectivities (up to 92 % yield and 99 % ee). The synthetic potential of this method was demonstrated by asymmetric synthesis of biological active compounds, such as (S)-PD172938 and (S)-Pazinaclone. The resulting chiral isoindolinones also serve as chiral ligands in cobalt-catalyzed enantioselective C-H annulation with alkynes to construct phosphorus stereocenter. A cobalt-catalyzed enantioselective C-H carbonylation with carbon monoxide as C1 source, enabling highly efficient synthesis of chiral isoindolinones, is reported. The robustness and synthetic potential of this method is demonstrated by asymmetric synthesis of bioactive molecules, (S)-PD172938 and (S)-Pazinaclone. Moreover, the chiral isoindolinones also proved to be efficient chiral ligands for asymmetric C-H activation.image