New Synthetic Methodologies to Access N-Heterocycles

获取 N-杂环的新合成方法

• 批准号: RGPIN-2014-05189
• 负责人: Spino, Claude
• 金额: $ 3.93万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632339
• 关键词: New; Synthetic; Methodologies; Access; Heterocycles

The proposed research falls in the category of synthetic organic chemistry, more specifically developing new reactions and methods of synthesis for application in natural products synthesis. We also propose to synthesize a new thermo- and photoresponsive scaffold to make molecular switches.The proposed research is divided in four parts, the first is concerned with developing a new (4+1)-cycloaddition reaction of chromium aminocarbenes (CAMCs) destined to make 5-membered N-heterocycles. The latter are molecular fragments ubiquitously found in natural alkaloids. The second part is a new twist to the Nobel-Prize winning ring-closing metathesis (RCM) reaction: we have found and would like to exploit a newly discovered reaction of CAMCs to make dienamines. Such fragments can be very useful to make more complex N-heterocyclic structures. The third part is concerned with the photochemical or thermal ring-contraction of N-activated lactams. It is also aimed at making N-heterocycles and ultimately natural alkaloids. We propose to study, develop, and expand each methodology. Mechanistic aspects of the reactions will be probed to better understand them and thus be better able to control reactivity and selectivity issues. We also propose to use each method in total synthesis of natural alkaloids as a way to underscore their usefulness.The last part of the proposed research is a venture into a new area of research in our laboratory. We believe we have discovered a new structural scaffold that could be used to make molecular switches. The scaffold is easily prepared and one such molecular scaffold, previously prepared for a totally different purpose, displayed the main attributes of a molecular switch: it isomerizes thermally and photochemically between two stable states. However, it needs to be studied and developed before we can call it a new thermo- and photoresponsive core structure. The synthesis is modular allowing for easy structural changes. We propose, at this stage, a proof of concept and will leave more complex studies and devices for a next discovery grant application.

建议的研究属于合成有机化学的范畴，更具体地说是开发新的反应和合成方法，用于天然产物的合成。我们还建议合成一种新型的热光响应支架来制作分子开关。我们的研究分为四个部分，第一部分是关于氨基卡宾铬(CAMC)的(4+1)-环加成反应，目的是生成5元N-杂环。后者是在天然生物碱中普遍存在的分子片段。第二部分是对诺贝尔奖获得者闭环歧化(RCM)反应的一个新的转折：我们已经发现并希望利用新发现的CAMCs反应来生成二烯胺。这样的片段可以非常有用地制造更复杂的N-杂环结构。第三部分是关于N-活化内酰胺的光化学或热环收缩。它的目标也是制造N-杂环，并最终制造天然生物碱。我们建议研究、开发和扩展每种方法。将探讨反应的机理方面，以更好地了解它们，从而更好地控制反应性和选择性问题。我们还建议在天然生物碱的全合成中使用每种方法，以强调它们的有效性。拟议研究的最后一部分是对我们实验室一个新研究领域的冒险。我们相信我们已经发现了一种新的结构支架，可以用来制造分子开关。这种支架很容易制备，其中一种以前为了完全不同的目的而制备的分子支架显示了分子开关的主要属性：它在两个稳定状态之间以热和光化学的方式异构化。然而，在我们可以称之为一种新的热光响应核心结构之前，它还需要研究和开发。合成是模块化的，允许轻松的结构变化。在这个阶段，我们建议对概念进行验证，并将更复杂的研究和设备留给下一次发现拨款申请。