Cascade Catalysis: From Alkynes to Polycycles

高效、快速地制备含环有机分子是有机化学家面临的重要挑战之一。这些分子的单对映体结构——也就是左右旋相关的两种镜像形式之一——是有机化学现代应用中同样重要的考虑因素。在本提案中，我们的目标是发展通过短合成路线制备多环体系的化学，并作为单个对映体（即不对称）。我们将通过使用钯催化剂来控制与炔（碳-碳三键）相连的环系统的形成来实现这一目标。在这个领域，我们的团队通过最近的一篇高知名度的出版物已经成为国际领先的团队，在这个项目中，我们打算扩大我们对这一反应原理的理解和使用，以制备复杂但从根本上有用的含氧和氮原子的环系统-杂环-这是许多药物和农用化学品的核心。在我们计划的化学中，炔不仅通过与钯催化剂的相互作用来调节环的形成，而且它本身也是一个有价值的官能团，在成环步骤之后可以经历广泛的有用的化学反应。我们打算利用炔的独特性质来探索其他环体系的形成。虽然我们期望这些过程能够成功，但更大的雄心和冒险是使用“级联”反应在一步中制备多个环，这种反应本质上比先前描述的单独反应序列具有更高的反应效率和产量-这一原则从根本上与EPSRC Dial-A-Molecule大挑战联系在一起。在这种情况下，我们建议研究的反应也形成各自的产物作为单一立体异构体（即单一的三维结构，其中存在几种可能性）。这一点很重要，因为在新药设计中的应用将依赖于这种选择性。该项目还旨在突破序列催化和双催化的界限，即多个催化反应直接连续发生，要么在单独的反应中（序列），要么在同一个反应烧瓶中（双催化）。这导致了更大的分子复杂性，但制备起始材料所需的步骤数量没有额外的成本，是催化研究的前沿领域。总之，我们的目标是采用新的和当代的催化过程，以灵活和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产品类型的广泛扩展，这将增强在药物化学，农用化学品，化学生物学和材料化学中的应用可能性。

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.