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 the Pd(OAc)(2)-catalyzed oxidative cyclization of (E)-4-hexenyltosylamide. Two of the ligands, DAF and 6,6'-dimethyl-2,2'-bipyridine (6,6'-Me(2)bpy), 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'-Me(2)bpy originates from the ability of these ligands to access kappa(1)-coordination modes via dissociation of one of the pyridyl rings. This hemilabile character is directly observed by NMR spectroscopy upon adding 1 equiv of pyridine to solutions of 1/1 L/Pd(OAc)(2) (L = DAF, 6,6'-Me(2)bpy) and is further supported by the X-ray crystal structure of Pd(py)(kappa(1)-DAF)OAc2. DFT computational studies illuminate the influence of three different chelating ligands (DAF, 6,6'-Me(2)bpy, and 2,9-dimethyl-1,10-phenanthroline (2,9-Me(2)phen)) on the energetics of the aza-Wacker reaction pathway. The results show that DAF and 6,6'-Me(2)bpy destabilize the corresponding ground-state Pd(N similar to N)(OAc)(2) complexes, while stabilizing the rate-limiting transition state for alkene insertion into a Pd-N bond. lnterconversion between, kappa(2) and kappa(1) coordination modes facilitates access to open coordination sites at the Pd-II center. The insights from these studies introduce new ligand concepts that could promote numerous other classes of Pd-catalyzed aerobic oxidation reactions.