Cascade Catalysis: From Alkynes to Polycycles

级联催化：从炔烃到多环化合物

• 批准号: EP/K005391/1
• 负责人: Edward Anderson
• 金额: $ 30万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK005391%2F1
• 关键词: Cascade; Catalysis; Alkynes; Polycycles

The efficient and rapid preparation of cyclic (ring-containing) organic molecules is one of the most important challenges for organic chemists. The construction of these molecules as single enantiomers - that is, one of two mirror image forms which are related as are left and right hands - is an equally vital consideration for modern applications of organic chemistry. In this proposal, we aim to develop chemistry which prepares multiple ring systems by short synthetic routes, and as single enantiomers (i.e asymmetrically).We will achieve this aim through the use of palladium catalysts to control the formation of ring systems which are connected to alkynes (carbon-carbon triple bonds). In this arena, our group has established itself as an internationally leading team through a recent high profile publication, and in this project we intend to expand our understanding and use of this reaction principle to prepare complex but fundamentally useful ring systems containing oxygen and nitrogen atoms - heterocycles - which form the core of many pharmaceuticals and agrochemicals.In our planned chemistry, the alkyne serves not only to mediate ring formation through its interaction with the palladium catalyst, but is also a valuable functional group in its own right which can undergo a wide range of useful chemistry after the ring-forming step. We intend to use the unique properties of the alkyne to explore the formation of additional ring systems.While we expect these processes to be successful, of greater ambition and adventure is the preparation of multiple rings in a single step using "cascade" reactions, processes which intrinsically lead to higher reaction efficiency and yields than the previously described separate reaction sequences - a principle which fundamentally links to the EPSRC Dial-A-Molecule Grand Challenge. The reactions we propose to study in this context also form their respective products as single stereoisomers (i.e. single three-dimensional structures where several possibilities exist). This is important, as applications in the design of new pharmaceuticals will rely on this selectivity.The project also aims to push boundaries in sequenced and dual catalysis - where multiple catalytic reactions take place in direct succession, either in separate reactions (sequenced) or more ambitiously and appealingly in the same reaction flask (dual catalysis). This leads to even greater molecular complexity but with no extra cost to the number of steps needed to prepare starting materials, and is an area at the forefront of catalysis research. In summary, we aim to employ new and contemporary catalytic processes to build molecules in a flexible and novel fashion. The variety of functional groups we intend to explore in these processes will lead to a broad expanse of product types, which will enhance possibilities for applications in medicinal chemistry, agrochemicals, chemical biology, and materials chemistry.

循环（含环）有机分子的有效和快速制备是有机化学家最重要的挑战之一。这些分子作为单个对映异构体的构造 - 即，左手和右手相关的两种镜像形式之一 - 是有机化学现代应用同样重要的考虑因素。在该提案中，我们旨在开发通过短合成路线来制备多个环系统的化学性能，并作为单个对映异构体（即不对称）。我们将通过使用钯催化剂来控制连接到Alkynes（碳 - 碳三键）的环系统的形成来实现这一目标。在这个领域，我们的小组通过最近的备受瞩目的出版物将自己确立为国际领先的团队，在这个项目中，我们打算扩大对该反应原则的理解和使用，以准备复杂但从根本上有用的环系统，这些环节含有氧气和氮原子 - 杂环 - 异性孢子 - 通过许多药物的核心形成我们的核心互动，而不是我们的核心互动。钯催化剂本身也是一个有价值的功能群，它可以在环形成步骤后经历各种有用的化学反应。 We intend to use the unique properties of the alkyne to explore the formation of additional ring systems.While we expect these processes to be successful, of greater ambition and adventure is the preparation of multiple rings in a single step using "cascade" reactions, processes which intrinsically lead to higher reaction efficiency and yields than the previously described separate reaction sequences - a principle which fundamentally links to the EPSRC Dial-A-Molecule Grand Challenge.我们建议在这种情况下研究的反应也形成了它们各自的产物作为单个立体异构体（即存在几种可能性的单个三维结构）。这一点很重要，因为新药物设计中的应用将依赖于这种选择性。该项目还旨在在顺序和双重催化中突破界限 - 在同一反应（序列）中，多次催化反应是直接连续的，或在相同的反应瓶中进行了更为雄心勃勃，更具吸引力的（双重催化）。这会导致更大的分子复杂性，但没有额外的成本来制备起始材料所需的步骤数，并且是催化研究最前沿的领域。总而言之，我们旨在采用新的和现代的催化过程以灵活而新颖的方式构建分子。我们打算在这些过程中探索的各种官能团将导致广泛的产品类型，这将增强药物化学，农业化学，化学生物学和材料化学的应用的可能性。

项目成果

Computational ligand design in enantio- and diastereoselective ynamide [5+2] cycloisomerization.

• DOI: 10.1038/ncomms10109
• 发表时间: 2016-01-05
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Straker RN;Peng Q;Mekareeya A;Paton RS;Anderson EA
• 通讯作者: Anderson EA

Selectivity in Transition Metal-catalyzed Cyclizations: Insights from Experiment and Theory.

过渡金属催化环化的选择性：实验和理论的见解。

• DOI: 10.2533/chimia.2018.614
• 发表时间: 2018
• 期刊: Chimia
• 影响因子: 1.2
• 作者: Anderson EA

Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindoles.

• DOI: 10.1039/c5cc08886k
• 发表时间: 2016-01
• 期刊: Chemical communications
• 影响因子: 4.9
• 作者: V. Chintalapudi;E. Galvin;Rebecca L. Greenaway;Edward A. Anderson