Development of palladium(II)-catalyzed methods for alkene functionalization: Intermolecular oxidative alkylation and intra- and intermolecular oxidative amination

The development of palladium-catalyzed methods for the oxidative formation of new carbon-carbon and carbon-nitrogen bonds will be described herein. For the oxidative coupling of soft carbon nucleophiles with aryl olefins, the most effective catalyst identified was (CH3CN)2PdCl 2 in the presence of magnesium acetate. When developing the oxidative coupling of nitrogen nucleophiles with alkenes, two catalyst systems were identified. In the intermolecular oxidative amination, the catalyst system developed utilized N-heterocyclic carbenes (NHCs) as ligands for palladium. The optimal catalyst system identified was IMesPd(O2CCF 3)2(OH2) in the presence of catalytic acetic or benzoic acid. The use of the NHC ligand in the presence of acid allowed the oxidative cyclization to occur under an air atmosphere instead of using pure molecular oxygen. Work was then initiated to extend the scope of this chemistry toward developing an asymmetric variant of the cyclization. Development of an asymmetric oxidative cyclization focused on the use of chiral carboxylates and NHCs and ligands to induce asymmetry. Work on intermolecular oxidative amination focused on developing conditions where the alkene was employed as the limiting reagent, and on expanding the alkene scope. The optimal catalyst system identified for this transformation was Pd(OAc)2 in benzonitrile at 4 atm of molecular oxygen to help prevent catalyst decomposition.