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′-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 1 equiv of pyridine to solutions of 1/1 L/Pd­(OAc)2 (L = DAF, 6,6′-Me2bpy) and is further supported
by the 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 facilitates 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 reactions.