Enantioselective C-H Amination of Alkenes and Carbonyl Compounds and Novel Application Thereof

烯烃和羰基化合物的对映选择性C-H胺化及其新应用

• 批准号: 9171207
• 负责人: Radhey S Srivastava
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF LOUISIANA AT LAFAYETTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171207
• 关键词: Algorithms; Alkaloids; Alkenes; Amination; Amines; Amino Acids; Antiepileptic Agents; Area; Chemicals; Complex; Copper; Detection; Development; Drug Compounding; Future; Goals; Hydroxylamine; In Situ; Individual; Kinetics; Learning; Ligands; Light; Metals; Methods; Modification; Natural Product Drug; Natural Products; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Phosphines; Process; Reaction; Reporting; Research; Research Personnel; Route; Suggestion; Synthesis Chemistry; System; Techniques; Testing; Vigabatrin; Work; X-Ray Crystallography; adduct; base; beta-Lactams; carbonyl compound; catalyst; chiral molecule; cholesterol absorption; design; docetaxel; experience; ezetimibe; inhibitor/antagonist; next generation; novel; novel strategies; oxindole; pharmacophore; practical application; research study; screening; small molecule; small molecule therapeutics; tertiary amine; tool

Project Summary: The general aim of the project is to develop synthetic methods of broad utility and function that will ultimately provide new chemical tools for the diverse range of synthetic chemists and biomedical researchers that utilize chiral amines and chiral N- heterocycles. The main objective is to invent new catalytic asymmetric amination methods that allow enantioselective access to chiral allyl amines and α-amino carbonyls. As a consequence, this core research will prove valuable to a number of wide-ranging industrial areas. During the project period, the PIs plan to demonstrate the value of this new chemical strategy in the context of first examples of catalytic enantioselective aminations and their application to access valuable chiral molecules. Individual goals of the proposed research include: (i) Developing a novel approach for the synthesis of chiral allyl amines, (ii) Synthesis of important chiral N-aryl β-alkyl Aza Baylis-Hillman (ABH) adducts which were not yet reported because of substrate scope limitation of classical ABH reactions; (ii) As metal-nitroso intermediates are moderately thermally stable, it will be possible to elaborate the mechanisms of asymmetric allylic amination, to learn the best ways to design and synthesize practical efficient catalysts; thus, shedding light on the mechanism of these asymmetric nitrogenation reactions; (iii) Total synthesis of a hydroxymethyl docetaxel fragment, (iv) Asymmetric synthesis of β-aminoacids and β-lactams, (v) Synthesis of the cholesterol absorption inhibitor Ezetimibe, (vi) Antiepileptic drug Vigabatrin, (vii) Asymmetric α C-H amination of carbonyl compounds, and (viii) Asymmetric α C-H amination of oxindoles. These new strategies provide a practical solution to access novel synthetic targets and should allow for future advances in the fields of asymmetric amination and group transfer reactions.

项目概要： 该项目的总体目标是开发具有广泛实用性的合成方法， 功能，最终将提供新的化学工具，为各种合成 化学家和生物医学研究人员利用手性胺和手性N- 杂环主要目的是发明新的催化不对称胺化反应 允许对映选择性地获得手性烯丙基胺和α-氨基羰基的方法。 因此，这项核心研究将证明对一些广泛的 工业区。在项目期间，PI计划证明此 新的化学策略的催化对映选择性的第一个例子的背景下， 胺化及其在获得有价值的手性分子中的应用。 拟议研究的个人目标包括：（一）开发一种新的 手性烯丙基胺的合成方法，（ii）重要的手性N-芳基的合成 β-烷基氮杂Baylis-Hillman（ABH）加合物，由于 经典ABH反应的底物范围限制;（ii）作为金属亚硝基中间体 是适度的热稳定，这将是可能的阐述机制， 不对称烯丙基胺化，学习设计合成实用的最佳途径 有效的催化剂;因此，阐明这些不对称的机制， （iii）羟甲基多西他赛片段的全合成，（iv） β-氨基酸和β-内酰胺的不对称合成（v）胆固醇的合成 吸收抑制剂依折麦布，（vi）抗癫痫药物氨己烯酸，（vii）不对称α C-H 羰基化合物的胺化，和（viii）羟吲哚的不对称α C-H胺化。 这些新的策略提供了一个实用的解决方案，以获得新的合成目标， 应考虑到未来在不对称胺化和基团转移领域的进展 反应.