AZACYCLIC SYNTHESIS USING N-SULFONYLOXY AMINES

提出了以利用N-磺酰氧基为目标的研究方案 胺(NSA)作为可发生分子内反应的亚胺离子的前体 环化成氮杂环产物。拟议的研究将调查 使用N-氧化前驱体形成亚胺离子的另一种方法， 而不是在正常的基于曼尼希的方法中使用的C-氧化前体 亚胺离子的形成。我们并不打算提供替代产品 基于曼尼希产生的亚胺离子，因为它往往是最 成功且最佳地进入亚胺离子环化反应。然而，在某些情况下 基于曼尼奇的化学不太成功或不太方便的情况 亚胺离子的产生。正是对于这些案件，新的 必须找到形成金属离子的方法。我们对美国国家安全局的研究超过了 在过去的几年里，人们一直在用来精确地确定NSA可能提供的 这些问题领域的独特解决方案。因此，新的战略 氮杂环天然产物的合成可能会出现。 我们想要证明在国家安全局阳离子碳向氮的迁移 提供了一种新的概念方法来准备和捕获 亚胺离子。NSA的两种特殊迁移反应--扩环 和氢化物迁移，将被用作建设 氮杂环化合物。这两个过程，在适当的底物中，产生 可随后进行分子内捕获的亚胺离子 氮环的形成。三个特定的重新排列过程提供了 全神贯注于工作。(A)碳环到氮环的串联膨胀- 分子内环化将作为一种生产手段进行研究。 直接生产多环产品。(B)叔胺中的氢化物重排 国家安全局的衍生物将作为一种简单的内环亚胺的途径进行研究 离子。(C)异羟肟酸NSA衍生物中的氢化物重排将 用来产生N-酰亚胺离子。 这些努力的一个主要推动力是强大的生理 许多产品的活跃度。范围广泛的活动，包括 强心作用，组织坏死，抗癌行为，以及 在生物碱产品中可以发现抗菌活性。亚胺离子 从而在大量重要化合物的合成中起着重要的作用 生理活性物质。NSA在氮杂环化合物中的应用 这里提出的综合是一种新的方法论。新的综合策略 具有生理活性的氮杂环目标的开发特别是 重点放在传统合成技术存在问题的系统上 战略。

A program of research is proposed whose goal is to utilize N-sulfonyloxy amines (NSA) as precursors for iminium ions that can undergo intramolecular cyclization to azacyclic products. The proposed research will investigate a different approach to iminium ion formation using N-oxidized precursors, rather than C-oxidized precursors used in normal Mannich-based methods of iminium ion formation. It is not our intention to offer a replacement for Mannich-based generation of iminium ions, since it is often the most successful and best entry into iminium ion cyclizations. However, in some cases Mannich-based chemistry is less successful or less convenient for the generation of iminium ions. It is precisely for these cases that new methods of iminium ion formation must be found. Our studies on NSA over the last several years have been used to pinpoint how NSA might offer unique solutions in these problem areas. As a result, new strategies for the synthesis of azacyclic natural products could emerge. We wish to demonstrate that cationic carbon to nitrogen migration in NSA provides a new conceptual approach to the preparation and trapping of iminium ions. Two particular migration reactions of NSA, ring expansion and hydride migration, will be used as focal points for the construction of azacyclic compounds. These two processes, in appropriate substrates, yield iminium ions which can undergo subsequent intramolecular trapping and azacycle formation. Three specific rearrangement processes provide the focus for the work. (a) Tandem carbon to nitrogen ring expansion- intramolecular cyclization will be investigated as a means of producing multicyclic products directly. (b) Hydride rearrangement in tertiary amine NSA derivatives will be examined as a route to simple endocyclic iminium ions. (c) Hydride rearrangement in hydroxamic acid NSA derivatives will be utilized to generate N-acyl iminium ions. A major driving force for these efforts is the potent physiological activity of many of the products. A wide spectrum of activities including cardiotonic effects, tissue necrosis, anticarcinogenic behavior, and antibiotic activity can be found in the alkaloid products. Iminium ions thus play an important role in the synthesis of a large number of important physiologically active agents. The utilization of NSA for azacyclic synthesis proposed here is a new methodology. Fresh synthetic strategies to physiologically active azacyclic targets are developed with particular emphasis on systems that are problematic by traditional synthetic strategies.