Regiocontrolled Intermolecular Hydroamination of Olefins

烯烃的区域控制分子间氢胺化

• 批准号: 8509524
• 负责人: Sarah Marie Bronner
• 金额: $ 4.92万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2014-07-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509524
• 关键词: Address; Agrochemicals; Alkenes; Amides; Amination; Amines; Antidepressive Agents; Antihistamines; Antipsychotic Agents; Applications Grants; Biological Factors; Carbon; Catalysis; Chemicals; Chlorpheniramine; Complement; Decongestants; Development; Drug Industry; Dyes; Ephedrine; Felis catus; Goals; Hydrogenation; Imines; Literature; Medicine; Methodology; Methods; Names; Nitrogen; Pharmaceutical Preparations; Phase; Phenylephrine; Prevalence; Production; Reaction; Research; Route; Solvents; Structure; Synthroid; System; Therapeutic; Thyroid preparation; Tranquilizing Agents; Urinary Incontinence; Variant; Waste Products; chemical synthesis; functional group; innovation; psychostimulant; ropinirole

DESCRIPTION (provided by applicant): Amines are ubiquitous in the pharmaceutical industry. In fact, 152 out of the top 200 brand name drugs in the US in 2010 contain amine or amide functionalities. Notable examples of amine-containing drugs include the antihistamine, chlorpheniramine, and the decongestants, ephedrine and phenylephrine. Due to the enormous prevalence of amines in therapeutics, as well as in the production of dyes, solvents, agrochemicals, and commodity and fine chemicals, the formation of carbon-nitrogen bonds is of paramount importance. Hydroamination is an attractive method to install the amine functionality, and may complement and may even prove more useful than existing methodologies that often produce stoichiometric waste products, require drastic reaction conditions, or rely on expensive starting materials. The proposed research aims to develop a formal hydroamination methodology that would allow access to linear amines from readily available terminal olefin starting materials. This transformation has been historically challenging because of the tendency of nucleophiles to add into olefins with Markovnikov selectivity. This new strategy would rely on a relay system that would couple three different catalytic cycles. Additionally, construction of branched amines in both racemic and enantioenriched form is described using an analogous approach. Overall, the formal hydroamination strategies proposed should offer alternative and concise methods of constructing medicinally privileged amines from readily accessible olefin starting materials.

描述(申请人提供)：胺在制药行业中普遍存在。事实上，2010年美国最大的200种品牌药物中，有152种含有胺或酰胺功能。显著的含胺药物包括抗组胺药、扑尔敏，以及减充血剂麻黄素和苯肾上腺素。由于胺在治疗学以及染料、溶剂、农用化学品、商品和精细化学品生产中的广泛使用，碳-氮键的形成是至关重要的。氢胺化是一种很有吸引力的安装胺功能的方法，可能是对现有方法的补充，甚至可能比现有方法更有用，这些方法通常会产生化学计量废物，需要激烈的反应条件，或依赖昂贵的起始材料。拟议的研究旨在开发一种正式的氢胺化方法，使人们能够从容易获得的端烯烃原料中获得直线胺。这种转变在历史上一直具有挑战性，因为亲核试剂倾向于以马尔可夫尼科夫选择性添加到烯烃中。这一新战略将依赖于一个接力系统，该系统将耦合三个不同的催化循环。此外，使用类似的方法描述了外消旋和富含对映体的支化胺的结构。总体而言，提出的正式氢胺化策略应该提供替代和简明的方法，从容易获得的烯烃原料中构建具有药用特权的胺。