Amination and Etherification of Aryl Halides and Olefins

描述(申请人提供)：这项研究计划包括钯催化的芳基卤化物的胺化和醚化，以及钯催化的烯烃的氢胺化。在前一个赠款期间的研究导致了一些最活跃的催化剂，用于钯催化的胺化和醚化，包括三种不同的催化剂，已出售或在商业上使用。在未发表的工作中，我们在与最活跃的催化剂的反应中分离了真正的氨基和烷氧基中间体，并获得了初步结果，这些结果表明可以解决杂芳烃底物的胺化和醚化反应，这通常会毒害或延缓最活跃的钯催化剂的芳胺化活性。我们还发现了用于双烯和乙烯与芳香胺和脂肪胺的氢胺化反应的钯催化剂，并找到了双烯高对映选择性氢胺化的条件。我们已经揭示了钯催化的氢胺化反应的机理，并分离了与胺反应生成氢胺化产物的中间体。最近，我们发现了第一个由Ru配合物催化的烯烃氢胺化反应，拟议的研究范围将扩大到包括这些用于氢胺化反应的新型催化剂。这项申请要求重新支持最近开发的用于每一种反应的催化剂的研究。我们将研究芳基氯化物和对甲苯磺酸盐的催化胺化和醚化反应机理。这些研究将包括揭示新的三配位氨基和烷氧基配合物的化学，以及研究由反应速度对碱和卤素浓度的依赖而导致的络合动力学行为。此外，我们还将研究基于配位结构的配体与受阻的二烷基膦取代基的反应，这将增加偶联的范围，并应延长催化剂的寿命。这种配体的结构可以生成快速氧化加成的钯配合物，但可以抵抗胺或碱性杂环的置换。此外，我们还将研究我们所发现的氢胺化反应的范围和机理。我们将研究不同的配体结构对钯催化的乙烯基芳烃氢胺化反应的速率和选择性的影响，并将描述Ru催化反应的基本步骤。最近发现的钯催化剂表现出比原始体系更高的活性，我们将研究这些配合物催化的反应的官能团耐受性。此外，我们将努力创造条件，在乙烯基芳烃中添加其他氮底物，并在更多取代的乙烯基芳烃和单烯基烯中添加胺。

DESCRIPTION (provided by applicant): This research program encompasses palladium-catalyzed amination and etherification of aryl halides and palladium-catalyzed hydroamination of olefins. Studies during the previous grant period led to some of the most active catalysts for the palladium-catalyzed amination and etherification, including three different catalysts sold or used commercially. In unpublished work, we have isolated the true amido and alkoxo intermediates in reactions with the most active catalysts and have gained initial results that suggest a solution to the amination and etherification of heteroaromatic substrates, which typically poison or retard the activity of the most active palladium catalysts for aryl amination. We have also found palladium catalysts for the hydroamination of dienes and vinylarenes with both aromatic and aliphatic amines and have found conditions for highly enantioselective hydroamination of dienes. We have uncovered the mechanism for palladium-catalyzed hydroamination and have isolated the intermediate that reacts with amine to form the hydroamination product. Most recently, we discovered the first hydroamination of olefins catalyzed by ruthenium complexes, and the scope of the proposed research will expand to include these new catalysts for hydroamination. This application requests renewed support for studies of recently developed catalysts for each of these reactions. We will investigate the mechanisms of catalytic amination and etherification of aryl chlorides and tosylates. These investigations will include studies to reveal the chemistry of new three-coordinate amido and alkoxo complexes and studies to unravel the complex kinetic behavior that results from a dependence of the reaction rate on the concentration of base and halogen. In addition, we will investigate reactions with ligands based on a chelating structure with hindered dialkylphosphino substituents that will increase the scope of the couplings and should increase the lifetimes of the catalysts. The structure of this ligand generates palladium complexes that undergo fast oxidative addition but resist displacement by amines or basic heterocycles. In addition, we will investigate the scope and mechanism of the hydroamination reactions we have discovered. We will investigate the effects of varying ligand structure on the rates and selectivities of the palladium-catalyzed hydroamination of vinylarenes and will delineate the basic steps of the ruthenium-catalyzed reactions. With recently identified palladium catalysts that display higher activities than those of the original systems, we will investigate the functional group tolerance of the reactions catalyzed by these complexes. In addition, we will strive to develop conditions to add other nitrogen substrates to vinylarenes and to add amines to more substituted vinylarenes and simple alkenes.