Medium Ring Heterocycles by Directed C-C Bond Activation

通过定向 C-C 键活化制备中环杂环

• 批准号: 1792769
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1792769
• 关键词: Medium; Ring; Heterocycles; Directed; Bond

Our group develops new catalysis platforms that allow the rapid generation of pharmaceuticallyvaluable heterocyclic scaffolds. We have reported a range of (3+1+2) cycloadditions involvingamino-substituted cyclopropanes, where carbonyl directing groups facilitate oxidative insertion ofrhodium and CO to provide rhodacyclopentanone intermediates. These can be trapped by tetheredalkynes or alkenes to deliver the targets. Recently, we have extended this catalysis platform toprovide medium ring systems. Here, carbonyl directed insertion of Rh/CO is followed by alkeneinsertion and fragmentation to the targets. Note that aminocycloprapanes are readily available byCurtius rearrangement of the corresponding cyclopropane carboxylic acid, which in turn can beaccessed directly using a number of established methodologies. Methodologies that provide mediumring heterocycles allow access to unexplored regions of structural space and are therefore highlyvalued by medicinal chemists. In this project we will (a) expand our approach to provide new,distinct medium ring methodologies (Part 1) and (b) apply the chemistry in to a total synthesis of astructurally challenging natural product (Part 2).

我们的团队开发了新的催化平台，可以快速生成具有药用价值的杂环支架。我们报道了一系列氨基取代环丙烷的（3+1+2）环加成反应，其中羰基导向基团促进铑和CO的氧化插入，得到铑环戊酮中间体。这些可以被束缚的炔或烯烃捕获以递送靶。最近，我们已经扩展了这个催化平台，以提供中环系统。在这里，Rh/CO的羰基定向插入之后是烯烃插入和片段化到靶。注意，氨基环丙烷可以通过相应的环丙烷羧酸的Curtius重排容易地获得，这反过来又可以使用许多已建立的方法直接获得。提供中环杂环的方法允许进入未探索的结构空间区域，因此受到药物化学家的高度重视。在这个项目中，我们将（a）扩展我们的方法，以提供新的，独特的中环方法（第1部分）和（B）应用化学在全合成的结构具有挑战性的天然产物（第2部分）。

项目成果

Rhodacyclopentanones as Linchpins for the Atom Economical Assembly of Diverse Polyheterocycles.

• DOI: 10.1021/jacs.9b12421
• 发表时间: 2020-01
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Gang‐Wei Wang;Olivia Boyd;Tom A. Young;Sophie M. Bertrand;J. Bower