Diazafluorenone-Promoted Oxidation Catalysis: Insights into the Role of Bidentate Ligands in Pd-Catalyzed Aerobic Aza-Wacker Reactions.

2,2'-Bipyridine (bpy), 1,10-phenanthroline (phen) and related bidentate ligands often inhibit homogeneous Pd-catalyzed aerobic oxidation reactions; however, certain derivatives, such as 4,5-diazafluoren-9-one (DAF), can promote catalysis. In order to gain insight into this divergent ligand behavior, eight different bpy- and phen-derived chelating ligands have been evaluated in Pd(OAc)2-catalyzed oxidative cyclization of (E)-4-hexenyltosylamide. Two of the ligands, DAF and 6,6'-dimethyl-2,2'-bipyridine (6,6'-Me2bpy), support efficient catalytic turnover, while the others strongly inhibit the reaction. DAF is especially effective and is the only ligand that exhibits "ligand-accelerated catalysis". Evidence suggests that the utility of DAF and 6,6'-Me2bpy originates from the ability of these ligands to access κ1-coordination modes via dissociation of one of the pyridyl rings. This hemilabile character is directly observed by NMR spectroscopy upon adding one equivalent of pyridine to solutions of 1:1 L/Pd(OAc)2 (L = DAF and 6,6'-Me2bpy), and is further supported by an X-ray crystal structure of Pd(py)(κ1-DAF)OAc2. DFT computational studies illuminate the influence of three different chelating ligands [DAF, 6,6'-Me2bpy, and 2,9-dimethyl-1,10-phenanthroline (2,9-Me2phen)] on the energetics of the aza-Wacker reaction pathway. The results show that DAF and 6,6'-Me2bpy destabilize the corresponding ground-state Pd(N~N)(OAc)2 complexes, while stabilizing the rate-limiting transition state for alkene insertion into a Pd-N bond. Interconversion between κ2- and κ1-coordination modes facilitate access to open coordination sites at the PdII center. The insights from these studies introduce new ligand concepts that could promote numerous other classes of Pd-catalyzed aerobic oxidation reaction.