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）本提案描述了免费 自由基介导的芳基和乙烯基胺化反应合成吲哚啉， 吡咯烷杂环。由于pH中性条件 从测量结果来看，该技术比大多数替代方法都要上级 化学选择性。该策略在概念上的不同之处在于， 胺中的氮碳π键代替氮-氢参与 σ键活化为了完成胺化，碳自由基被 区域选择性地加到甲亚胺的氮上。至于碳， 已知自由基有效地添加到各种 由于含有偶氮甲环的官能团，所述的加成是高度 非常规的，几乎没有先例的。温和的反应条件为： 特别适合于结构复杂和高度复杂的 用于靶向合成的官能化中间体。使用 自由基中间体还允许开发串联键形成过程。 自由基介导的芳基胺化反应的发展扩展到收敛 吲哚啉环化策略。这些过程的独特之处在于， 对映选择性地构建二氢吲哚杂环，包括α-氨基 acids.为了说明此方法的一些重要特性， 提出了一种新的吲哚生物碱的全合成方法， 不存在合成路线。 自由基介导的乙烯基胺化的发展包括使用 烯胺产物作为制备官能化吡咯烷的中间体。的 这些吡咯烷基烯胺的重要性通过会聚和 不存在对映选择性的nat-丝裂霉素C的简便合成 目前存在。