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广泛探索的领域。最常见的是，金属介导的转化正被应用于获得越来越多样化和理想的结构框架，并通过减少步骤。与此相关，Pauson-Khand反应（PKR）是一种强大而有效的技术，在天然产物和其他环状化合物的合成中作为关键转化的应用越来越多。已经说明了这一点，在新兴的方法中，底物范围仍然有些有限，其中衍生自标准炔和（最常见的是应变的）烯烃组分的双环基序最容易制备。更具体地并且关于该环加成反应的烯烃组分，存在非常少的更多官能化配偶体的实例，例如含有额外杂原子的那些，其提供了具有潜在药学有用功能的更多样化的环戊烯酮产品。Kerr和GSK合作伙伴之间的这项合作计划将为Pauson探索新的含杂原子的底物，Khand环化反应以构建一系列修饰的环戊烯酮产物。这些方法将提供一系列灵活和强大的技术，以允许获得各种药学上所需的有机化合物和天然产物，同时增加反应的总体能力。作为总体工作方案的一部分，将使用计算驱动的方法来加深对反应机理和催化剂设计的理解，并扩大新兴反应的范围。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.