New metal-mediated cyclisation methods for the generation of heteroatom functionalised polycyclic systems.

以直接和有效的方式制备适当官能化的多环体系是有机合成中一个被广泛探索的领域。最常见的是，金属中介的转变正在被应用于获得越来越多样化和更理想的结构框架，并且通过更少的步骤。在这方面，Pauson-Khandd反应(PKR)代表了一种强大而有效的技术，它在合成天然产物和其他环状化合物中被越来越多地用作关键转化。话虽如此，在新兴的方法中，底物的范围仍然有些有限，最容易制备的是从标准炔烃和(通常是张力的)烯烃组分衍生的双环基元。更具体地说，关于这种环加成反应的烯烃成分，很少有更官能化的合作伙伴的例子，例如那些包含额外杂原子的合作伙伴，这些合作伙伴提供了更多样化的具有潜在药用功能的环戊酮产品。这项由Kerr和GSK合作伙伴之间的合作计划将为Pauson-Khand环化反应探索新的含有杂原子的底物，以构建一系列装饰的环戊酮产品。这种方法将提供一系列灵活而强大的制备技术，使人们能够获得各种药物所需的有机化合物和天然产品，同时提高反应的整体能力。作为总体工作方案的一部分，将使用计算驱动的方法加强对反应机理和催化剂设计的了解，并扩大新出现的反应范围。EPSRC的主要研究领域是催化、化学反应动力学和机理以及合成有机化学。

The preparation of suitably functionalised polycyclic systems in a direct and efficient manner is a widely explored area within organic synthesis. Most commonly, metal-mediated transformations are being applied to access increasingly more diverse and desirable structural frameworks, and through a reduced number of steps. In relation to this, the Pauson-Khand reaction (PKR) represents a powerful and effective technique, which has found increasing use as the key transformation in the synthesis of natural products and other cyclic compounds. Having stated this, within the emerging methods, the substrate scope remains somewhat limited, with bicyclic motifs derived from standard alkyne and (most often strained) alkene components being most readily prepared. More specifically and with regards to the alkene component of this cycloaddition reaction, there are very few examples of more functionalised partners, such as those containing additional heteroatoms, which provide more diverse cyclopentenone products with potentially pharmaceutically useful functionality.This collaborative programme between Kerr and GSK partners will explore novel heteroatom containing substrates for the Pauson-Khand cyclisation reaction to construct an array of decorated cyclopentenone products. Such methods will deliver a preparatively flexible and powerful range of techniques to allow access to a variety of pharmaceutically-desired organic compounds and natural products, all whilst increasing the overall capacity of the reaction. As part of the overall programme of work, computationally-driven methods will be used to deliver enhanced understanding of reaction mechanism and catalyst design, as well as the expansion of emerging reaction scope. The main EPSRC research areas addressed are Catalysis, Chemical Reaction Dynamics and Mechanism, and Synthetic Organic Chemistry.