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：（由申请人提供）该提案描述免费 自由基介导的芳基和乙烯基胺化反应，对吲哚素合成和 吡咯胺杂环分别。凭借pH中性条件 涉及，该技术优于大多数替代方法 化学选择性。策略在概念上有所不同 胺中的氮碳PI键代替氮 - 氢气 Sigma键激活。为了完成胺化，碳自由基是 区域选择性地添加到偶氮胺的氮中。就碳而言 众所周知，自由基有效地增加了各种碳 Azomethinecontaging官能团，所描述的添加是高度的 规定，几乎没有先例。轻度反应条件是 非常适合结构复杂且高度的转化 用于目标综合的功能化中间体。使用 自由基中间体还允许发展串联键合过程。 自由基介导的芳基胺化的发展扩展到收敛 吲哚环状策略。这些过程在它们的能力上是独一无二的 对映选择性构建吲哚线杂环，包括α-Amino 酸。为了说明该方法的一些重要特征，一个 总合成是由歧义吲哚生物碱成员的 不存在合成路线。 自由基介导的乙烯基胺的发展包括使用 Enamine产品作为中间体朝向功能化的吡咯烷。这 这些吡咯烷酰谜的重要性由收敛性和 NAT-肌霉素C的简明合成，没有对映选择性合成 目前存在。