Enantioselective Synthesis of Isoindolones via Palladium - Catalyzed Intramolecular Heck-Mizoroki Reactions of Endocyclic Enamides Using N,N-Ligands

The enantioselective synthesis of isoindolones via Heck-Mizoroki reactions of endocyclic enamides using a palladium-bis(oxazoline) catalyst system is described. The N,N-ligands, which are under-represented in palladium-catalyzed reactions involving aryl halides, proved to be an effective and low-cost alternative to their phosphine-based chiral ligand counterparts. The intramolecular Heck reaction of aryl iodides and endocyclic enamides enabled the construction of tricyclic isoindolones containing tertiary and quaternary chiral centers under mild conditions in yields up to 73 % and enantiomeric ratios up to 97 : 3. Vibrational circular dichroism (VCD) was instrumental in determining the absolute configuration of the enantioenriched isoindolones.