Amination and Etherification of Aryl Halides and Olefins

芳基卤化物和烯烃的胺化和醚化

• 批准号: 6868717
• 负责人: John F Hartwig
• 金额: $ 34.47万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868717
• 关键词: amides; amination; catalyst; chelating agents; chemical bond; chemical kinetics; chemical synthesis; ligands; metal complex; phosphines; ruthenium; stereochemistry

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 In unpublished work, we have isolated the true amido and alkoxo intermediates in reactions with the most active catalysts and have gained initial results that suggest a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

描述（由申请人提供）：该研究计划包括芳基卤化物的钯催化胺化和醚化以及烯烃的钯催化加氢胺化。在上一个资助期的研究导致了一些最活跃的催化剂的钯催化胺化和醚化，包括三种不同的催化剂出售或商业使用。在未发表的工作中，我们已经分离出真正的酰胺基和烷氧基中间体与最活跃的催化剂的反应，并已获得初步结果，提出了一个解决方案的胺化和醚化的杂芳族底物，通常中毒或延迟的活性最活跃的钯催化剂的芳基胺化。我们还发现了用于二烯和乙烯基芳烃与芳族和脂族胺的加氢胺化的钯催化剂，并发现了二烯的高度对映选择性加氢胺化的条件。我们揭示了钯催化氢胺化反应的机理，并分离出了与胺反应形成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氢胺化反应，并且所提出的研究范围将扩展到包括这些用于氢胺化的新催化剂。本申请要求对最近开发的用于这些反应中的每一种的催化剂的研究给予新的支持。我们将探讨芳基氯和甲苯磺酸酯的催化胺化和醚化反应的机理。这些调查将包括研究，以揭示新的三配位酰胺和烷氧基配合物的化学和研究，以解开复杂的动力学行为，从依赖于碱和卤素的浓度的反应速率的结果。此外，我们将研究与配体的基础上的螯合结构与受阻的二烷基膦基取代基，这将增加耦合的范围，并应增加催化剂的寿命的反应。该配体的结构产生钯络合物，其经历快速氧化加成，但抵抗胺或碱性杂环的置换。此外，我们将调查的范围和机制的氢胺化反应，我们已经发现。我们将研究不同配体结构对钯催化乙烯基芳烃氢胺化反应的速率和选择性的影响，并描述钯催化反应的基本步骤。最近确定的钯催化剂，显示更高的活动比原来的系统，我们将调查这些配合物催化的反应的官能团的耐受性。此外，我们将努力开发条件，添加其他氮底物的乙烯基芳烃和添加胺更多取代的乙烯基芳烃和简单的烯烃。