AZACYCLIC SYNTHESIS USING N-SULFONYLOXY AMINES

提出了利用N-磺酰氧基 胺（NSA）作为亚胺离子的前体， 环化成氮杂环产物。 拟议的研究将调查 使用N-氧化前体形成亚胺离子的不同方法， 而不是在常规的基于曼尼希的方法中使用的C-氧化的前体， 亚胺离子形成。 我们无意提供替代品， 基于曼尼希的亚胺离子的产生，因为它通常是最重要的 成功和最好地进入亚胺离子环化。 但在一些 案例基于曼尼希的化学不太成功或不太方便， 生成亚胺离子。 正是针对这些情况， 必须找到形成亚胺离子的方法。我们对NSA的研究超过 在过去的几年里，美国国家安全局已经被用来确定如何提供 在这些问题领域的独特解决方案。 因此， 可能出现氮杂环天然产物的合成。 我们希望证明，阳离子碳氮迁移在国家安全局 提供了一个新的概念方法，准备和诱捕 亚胺离子。 NSA的两个特殊迁移反应，扩环 和氢化物迁移，将被用作建设的重点， 氮杂环化合物。 这两个过程，在适当的基板，产量 亚胺离子，其可以经历随后的分子内捕获， 氮杂环生成。 三种特定的重排过程提供了 专注于工作。 (a)串联碳氮环膨胀- 将研究分子内环化作为产生 多环产物直接。 (b)叔胺中的氢化物重排 NSA衍生物将被检查作为一个简单的内环亚胺的路线 离子。 (c)异羟肟酸NSA衍生物中的氢化物重排将是 用于产生N-酰基亚胺离子。 这些努力的一个主要驱动力是强大的生理 许多产品的活动。 广泛的活动，包括 强心作用、组织坏死、抗癌行为，以及 在生物碱产物中可以发现抗生素活性。 伊什利翁 因此在合成大量重要的 生理活性剂。 NSA在氮杂环化合物中的应用 本文提出的综合方法是一种新的方法。 新的合成策略 与生理活性氮杂环靶标的结合， 强调传统合成方法存在问题的系统 战略布局

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.