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的功能化多环体系是有机合成中广泛探索的领域。最常见的是，金属介导的转换正被应用于获得越来越多样化和理想的结构框架，并且通过减少步骤。与此相关，Pauson-Khand反应（PKR）是一种强大而有效的技术，作为天然产物和其他环状化合物合成的关键转化，它的应用越来越广泛。说到这一点，在新兴的方法中，衬底范围仍然有些有限，从标准炔和（通常是应变的）烯烃组分衍生的双环基序是最容易制备的。更具体地说，关于这个环加成反应的烯烃组分，很少有更功能化的伙伴的例子，例如那些含有额外杂原子的伙伴，它们提供更多样化的环戊酮产品，具有潜在的药用功能。克尔和葛兰素史克的合作伙伴将探索新的含杂原子底物，用于Pauson-Khand环化反应，以构建修饰环戊酮产品阵列。这些方法将提供一个灵活和强大的制备技术范围，允许获得各种药物所需的有机化合物和天然产物，同时增加反应的总体能力。作为整个工作计划的一部分，计算驱动的方法将用于提高对反应机理和催化剂设计的理解，以及扩大新兴反应范围。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.