Heteroatom Annulations: The Catalytic Synthesis of Heterocycles

杂环化合物的重要性怎么强调都不为过；在所有已知的有机化合物中，大约有一半含有杂环。这些化合物，无论是天然产物还是设计的分子，都对各种各样的生物过程负责，它们是大多数药物的特征。它们还被用作农用化学品、着色剂和新材料。杂环化合物的合成有着悠久而广泛的历史，许多经典的合成方法已经被开发出来，但仍然存在着重大的挑战，某些化合物类别仍然难以制备。现代发现化学也对合成路线提出了新的要求，要求通过简单的后期修饰快速获得相关结构。在本提案中，我们提出了一种新的方法，允许使用单一策略访问各种杂环系统。在此过程中，我们开辟了新的杂环前体类别，并允许访问传统上提出相当大挑战的结构。该方法结合了两种简单的已建立的变换，生成了一种强大的杂环合成新方法。该方法基于串联钯催化的使用，关键是允许从单一前驱体获得各种不同的杂环。我们还将演示如何使用这种新方法来制备极具挑战性的杂环靶系统。

The importance of heterocyclic compounds cannot be overstated; around one half of all known organic compounds contain a heterocyclic ring. These compounds, be they natural products or designed molecules, are responsible for an amazing variety of biological processes and they feature in the majority of pharmaceuticals. They are also used as agrochemicals, colourants and as new materials. The synthesis of heterocyclic compounds has a long and extensive history in which many classic syntheses have been developed, however significant challenges still remain, with certain compound classes remaining difficult to prepare. Modern discovery chemistry also places new demands on synthetic routes, requiring rapid access to related structures through simple late-stage modifications. In this proposal we present new methodology that allows access to a variety of heterocyclic systems using a single strategy. In the process we open new classes of heterocycle precursors and also allow access to structures that have traditionally presented considerable challenges.The proposed methodolgy combines two simple established transformations to generate a powerful new method for heterocycle synthesis. The method is based on the use of tandem palladium catalysis, and crucially allows a whole variety of different heterocycles to be accessed from a single class of precursor. We will also demonstrate how this new method can be used to prepared extremely challenging heterocyclic target systems.