New Aryl and Vinyl Amination Methods

新的芳基和乙烯基胺化方法

• 批准号: 6624259
• 负责人: Jeffrey Nicholas Johnston
• 金额: $ 24.55万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6624259
• 关键词: amination; chemical group; chemical synthesis; free radicals; indoles; nitrogenous heterocyclic compound; pyrrolidines; stereochemistry

DESCRIPTION: (provided by applicant) This proposal describes free radical-mediated aryl and vinyl amination reactions to synthesize indoline and pyrrolidine heterocycles, respectively. By virtue of the pH-neutral conditions involved, this technology is superior to most alternative methods by measures of chemoselectivity. The strategy differs conceptually in that activation of a nitrogen carbon pi bond in the amine is involved instead of nitrogen-hydrogen sigma bond activation. To accomplish amination, carbon radicals are regioselectively added to the nitrogen of the azomethine. In so far as carbon radicals are known to add efficiently to the carbon of a variety of azomethinecontaining functional groups, the additions described are highly nonconventional and nearly without precedent. The mild reaction conditions are uniquely well-suited to transformations of structurally complex and highly functionalized intermediates used in target-oriented synthesis. The use of radical intermediates also allows development of tandem bond-forming processes. The development of radical-mediated aryl amination is extended to convergent indoline annulation strategies. These processes are unique in their ability to enantioselectively construct indoline heterocycles, including alpha-amino acids. To illustrate some of the important characteristics of this method, a total synthesis is proposed of a member of the ambiguine indole alkaloids for which no synthesis route exists. The development of free radical-mediated vinyl amination includes use of the enamine products as intermediates toward functionalized pyrrolidines. The importance of these pyrrolidinyl enamines is demonstrated by the convergent and concise synthesis of nat-mitomycin C for which no enantioselective synthesis currently exists.

描述：(申请者提供)本建议书描述免费 自由基介导芳基和乙烯基胺化反应合成吲哚和 吡咯烷杂环。凭借pH中性的条件 从衡量标准来看，这项技术优于大多数替代方法。 化学选择性。该策略在概念上不同之处在于激活 胺中的氮碳pi键而不是氮-氢参与其中。 西格玛键激活。为了完成胺化，碳基是 区域选择性地添加到甲亚胺的氮中。就碳而言 众所周知，自由基能有效地增加各种化合物的碳 某些偶氮化合物含有官能团，所述的加成物高度 非常规的，几乎没有先例。温和的反应条件是 独一无二地非常适合于结构复杂和高度 用于目标导向合成的官能化中间体。对.的使用 自由基中间体也允许发展串联成键过程。 自由基介导芳胺化的研究进展 吲哚环化策略。这些过程的独特之处在于它们能够 对映体选择性地构建吲哚杂环，包括α-氨基 酸。为了说明此方法的一些重要特征，请使用 提出了一种全合成一种含二氢吲哚生物碱的方法。 不存在任何合成路线。 自由基介导的乙烯基胺化反应的发展包括使用 烯胺类化合物作为功能化吡咯烷的中间体。这个 这些吡咯烷基烯胺的重要性由聚合性和 无对映选择性合成NAT-丝裂霉素C的简捷合成 目前存在。