Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines

Ti 催化级联氢氨基烷基化作为制备复杂官能化胺的途径

• 批准号: 10750347
• 负责人: Zoua Pa Vang
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-18 至 2025-08-17
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10750347
• 关键词: Alkenes; Amines; Aniline; Biological; Catalysis; Complex; Development; Electrons; Kinetics; Ligands; Medicine; Methodology; Methods; Modern Medicine; Muscarinic Antagonists; Nitrogen; Organic Chemistry; Pharmacologic Substance; Play; Preparation; Productivity; Reaction; Reporting; Role; Route; Structure; Time; Titanium; Transition Elements; catalyst; density; diene; drug candidate; improved; innovation; method development; phosphoramidate; scaffold; theories; tool

Project Summary/Abstract Central to the development of medicine is organic chemistry and catalysis as it has permitted the discovery of new reactions and methods for the synthesis of key pharmaceutical components that will play a critical role in continuing the advancement of modern medicine. With the high presence of nitrogen atoms in drug candidates due to their high biological activity, it is crucial to develop new and innovative methods to synthesize and functionalize nitrogen-containing molecules. Recently, reactive titanium intermediates were used to explore second insertions of unsaturated species yielding useful nitrogen heterocycles. This proposal will focus on developing an efficient and one-step atom- economical Ti-catalyzed multicomponent, cascading hydroaminoalkylation reaction to produce β- cycloalkyl amines from dienes and amine/aniline substrates. This methodology has potential to be a valuable synthetic tool because β-cycloalkyl amines products are scaffolds present in pharmaceutical compounds such as cyclopentamine and propylhexedrine and in M3 muscarinic antagonist. Additionally, this method will provide a fundamental understanding of this new reaction class that can be extended into other cascading reactions to rapidly build molecule complexity.

项目摘要/摘要 医学发展的中心是有机化学和催化，因为它允许 发现新反应和合成关键药物组件的方法 在继续现代医学的进步中发挥关键作用。高度存在 氮原子由于其高生物学活性而在候选药物中的氮原子，开发新的和 综合和功能化含氮分子的创新方法。最近，反应性 钛中间人用于探索不饱和物种的第二插入，从而有用 氮杂环。该提案将着重于开发有效且一步的原子 经济的Ti催化的多组分，层叠的氢氨基烷基化反应产生β- 来自二烯和胺/苯胺底物的环烷基胺。这种方法有可能成为 有价值的合成工具，因为β-氯烷基胺产物是药物中存在的支架 在M3毒蕈碱拮抗剂中，诸如环戊胺和丙酰己胺等化合物。 此外，此方法将提供对这个新反应类别的基本理解 扩展到其他级联反应，以快速构建分子复杂性。