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.

2,2′-联吡啶（2,2′-Bipyridine, bpy）、1,10-邻菲啰啉（1,10-phenanthroline, phen）及相关双齿配体通常会抑制均相钯催化好氧氧化反应；然而部分衍生物，如4,5-二氮芴-9-酮（4,5-diazafluoren-9-one, DAF），却可促进催化过程。为深入探究这类配体行为的差异性，本研究在乙酸钯(II)（Pd(OAc)₂）催化的(E)-4-己烯基对甲苯磺酰胺氧化环化反应中，评估了8种不同的联吡啶与邻菲啰啉衍生螯合配体的作用效果。其中两种配体——DAF与6,6′-二甲基-2,2′-联吡啶（6,6′-dimethyl-2,2′-bipyridine, 6,6′-Me₂bpy）可实现高效的催化循环，其余配体则会强烈抑制该反应。DAF的催化活性尤为突出，是唯一表现出“配体加速催化”特性的配体。研究证据表明，DAF与6,6′-Me₂bpy的效用源于这类配体可通过解离其中一个吡啶环，形成κ1配位模式的能力。当向摩尔比为1:1的配体/乙酸钯(II)（配体为DAF或6,6′-Me₂bpy）溶液中加入1当量吡啶时，核磁共振波谱（NMR spectroscopy）直接观测到了这种半不稳定配位特性；而Pd(py)(κ1-DAF)(OAc)₂的X射线晶体结构进一步佐证了这一结论。密度泛函理论（DFT, Density Functional Theory）计算研究阐明了三种不同螯合配体（DAF、6,6′-Me₂bpy与2,9-二甲基-1,10-邻菲啰啉（2,9-dimethyl-1,10-phenanthroline, 2,9-Me₂phen））对氮杂-Wacker（aza-Wacker）反应路径能垒的影响。结果显示，DAF与6,6′-Me₂bpy会使对应的基态钯(II)双螯合配合物Pd(N∼N)(OAc)₂发生去稳定化，同时稳定烯烃插入Pd–N键的决速过渡态。κ2与κ1配位模式之间的互变，可促进钯(II)中心开放配位位点的生成。本研究得到的相关结论，为开发更多可应用于钯催化好氧氧化反应的新型配体设计理念提供了新思路。