Multiple Absolute Stereocontrol in Pd-Catalyzed [3+2] Cycloaddition of Oxazolidinones and Trisubstituted Alkenes Using Chiral Ammonium-Phosphine Hybrid Ligands

The development of a Pd-catalyzed highly enantio- and diastereoselective [3+2] cycloaddition of 5-vinyloxazolidinones and activated trisubstituted alkenes is described in detail. This protocol for the single-step construction of densely functionalized pyrrolidines with three contiguous stereocenters including vicinal quaternary stereocenters depends on the remarkable ability of phosphine ligands possessing a chiral ammonium ion to promote intermolecular cycloaddition reactions with a precise control of absolute stereochemistry. A series of control experiments show that a chiral ammonium phosphine hybrid ligand enabled the individual, yet simultaneous stereocontrol of each chiral center in the annulation reaction. The reaction mechanism is also discussed with particular focus on the stereodetermining processes.