Palladium-Catalyzed Enantioselective Isodesmic C-H Iodination of Phenylacetic Weinreb Amides

Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C-H functionalization is unknown and enantioselective direct iodination of inert C-H bond is very rare. Rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry. Herein, we report an unprecedented highly enantioselective isodesmic C-H functionalization to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with Pd-II catalysis. Importantly, further transformations of the enantioenriched products are readily available at the iodinated or the Weinreb amide position, paving the way of related studies for synthetic and medicinal chemists.

Automated summary

In this study, a highly enantioselective isodesmic C-H functionalization method was developed to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with Pd-II catalysis. The rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry, and further transformations of the enantioenriched products are readily available, opening up new possibilities for related studies in synthetic and medicinal chemistry.