Amination and Etherification of Aryl Halides and Olefins

描述（由申请人提供）：本研究项目包括钯催化芳基卤化物的胺化和醚化以及钯催化烯烃的氢胺化。在上一个资助期间的研究导致了一些最活跃的钯催化胺化和醚化催化剂，包括三种不同的催化剂销售或商业使用。在未发表的工作中，我们已经在最活跃的催化剂反应中分离出了真正的酰胺和烷氧基中间体，并获得了初步结果，提出了一种解决杂芳香底物的胺化和醚化的方法，这通常会毒害或延缓最活跃的钯催化剂的芳基胺化活性。我们还发现了钯催化剂与芳香和脂肪胺的二烯和乙烯烯的氢胺化，并发现了高度对映选择性的二烯的氢胺化条件。我们揭示了钯催化的氢胺化反应的机理，并分离了与胺反应形成氢胺化产物的中间体。最近，我们发现了钌络合物催化烯烃的第一个氢胺化反应，并且提出的研究范围将扩大到包括这些新的氢胺化催化剂。本申请要求对最近开发的这些反应的催化剂的研究给予新的支持。我们将研究芳酰氯和邻苯二甲酸酯催化胺化和醚化的机理。这些研究将包括揭示新的三坐标酰胺和烷氧配合物的化学性质，以及揭示碱和卤素浓度对反应速率的依赖所导致的复杂动力学行为的研究。此外，我们将研究基于螯合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，并应增加催化剂的寿命。这种配体的结构产生钯配合物，经过快速氧化加成，但抵抗胺或碱性杂环的位移。此外，我们将研究我们发现的氢胺化反应的范围和机制。我们将研究不同配体结构对钯催化乙烯烯氢胺化反应的速率和选择性的影响，并将描述钌催化反应的基本步骤。随着最近发现的钯催化剂显示出比原始系统更高的活性，我们将研究这些配合物催化反应的官能团耐受性。此外，我们将努力开发条件，在乙烯烯中添加其他含氮底物，并在更多取代的乙烯烯和简单烯烃中添加胺。

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 In unpublished work, we have isolated the true amido and alkoxo intermediates in reactions with the most active catalysts and have gained initial results that suggest a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.