Amination and Etherification of Aryl Halides and Olefins

描述（由申请人提供）：该研究项目包括钯催化的芳基卤化物胺化和醚化以及钯催化的烯烃加氢胺化。上一资助期间的研究产生了一些用于钯催化胺化和醚化的最活跃的催化剂，包括三种商业销售或使用的不同催化剂。在未发表的工作中，我们在与最活性催化剂的反应中分离出了真正的酰胺基和烷氧基中间体，并获得了初步结果，为杂芳族底物的胺化和醚化提供了解决方案，这通常会毒害或阻碍芳基胺化中最活跃的钯催化剂的活性。我们还发现了用于二烯和乙烯基芳烃与芳香族和脂肪族胺的加氢胺化的钯催化剂，并找到了二烯的高度对映选择性加氢胺化的条件。我们揭示了钯催化加氢胺化的机理，并分离了与胺反应形成加氢胺化产物的中间体。最近，我们发现了第一个由钌配合物催化的烯烃加氢胺化反应，并且拟议研究的范围将扩大到包括这些用于加氢胺化反应的新型催化剂。该申请要求对最近开发的每种反应催化剂的研究提供新的支持。我们将研究芳基氯和甲苯磺酸盐的催化胺化和醚化机制。这些研究将包括揭示新型三配位酰胺和烷氧基配合物化学性质的研究，以及揭示因反应速率对碱和卤素浓度的依赖性而产生的复杂动力学行为的研究。此外，我们将研究与基于带有受阻二烷基膦取代基的螯合结构的配体的反应，这将增加偶联范围并延长催化剂的寿命。该配体的结构产生钯络合物，该络合物经历快速氧化加成，但抵抗胺或碱性杂环的置换。此外，我们将研究我们发现的加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基芳烃氢胺化的速率和选择性的影响，并将描述钌催化反应的基本步骤。最近发现的钯催化剂比原始系统具有更高的活性，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，将其他氮底物添加到乙烯基芳烃中，以及将胺添加到更多取代的乙烯基芳烃和简单烯烃中。

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 In unpublished work, we have isolated the true amido and alkoxo intermediates in reactions with the most active catalysts and have gained initial results that suggest a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