New Transition Metal Catalysed Methods for Alkyl C-N Bond Formation

碳氮键（C-N键）的形成是有机化学中的一个重要过程，但在许多情况下，这是一项非常困难的任务。本研究计划的目标是提供涉及金属催化剂的新方法，用于特别具有挑战性的C-N键形成类型：第一部分。第一个领域将着眼于以分子内方式形成碳氮键。我们将研究碳原子与其他三个原子成键的情况，其中至少有一个是另一个碳原子。在这里，我们将开发一种从一个简单的烯烃前体形成这种类型的C-N键的方法。在这个领域，我们还将研究控制形成哪个碳氮键镜像的可能性。在碳氮键的碳原子连着另外三个不同基团的情况下，这个特殊的方面是相关的。第2部分。我们要看的第二个方面是以分子间的方式形成碳氮键。这些流程的开发将更具挑战性，我们将使用从第1部分获得的知识来帮助实现这一点。为了促进这些新方法，我们将研究一种特定的含氮有机功能的化学，它允许氧化还原中性C-N键形成过程；这与金属催化剂相结合，将作为氮的来源。新的C-N键形成反应最初将在系统中开发，该功能是与它反应的烯烃相同分子的一部分。当新的C-N键形成时，就会因此产生环状结构。随着我们对反应的理解的提高，我们将看到有机官能团和烯烃是否可以成为不同分子的一部分。这种类型的碳氮键形成预计将更具挑战性。选择这一研究领域是因为C-N键是生命结构（如氨基酸）和药物化合物的重要组成部分。通过发展这些新的反应，我们将提供方法，使化学家能够以更快、更有效的方式制造生物学上重要的分子。事实上，这些新的反应甚至可以使人们制造目前无法获得的分子。从长远来看，这项研究可以通过开发治疗疾病的药物或通过提供分子探针来了解生物过程，从而使更广泛的社会受益。此外，由于许多现有方法受到专利保护（例如Buchwald-Hartwig胺化），因此对新的C-N键形成工艺的内在需求可能会限制其在工业环境中的部署。该研究计划的各个方面之前已作为EPSRC CAF申请的一部分提交，该申请没有被PI接受，而是被皇家学会URF接受。

Forming bonds between carbon and nitrogen (C-N bonds) is an important process in organic chemistry but in many instances this represents a very difficult task. The goal of this research proposal is to provide new methods, which involve metal catalysts, for particularly challenging types of C-N bond formation: Part 1. The first area will look at is forming C-N bonds in an intramolecular fashion. We will investigate cases where the carbon atom is bonded to three other atoms, of which at least one is another carbon atom. Here, we will develop a method which forms this type of C-N bond from a simple alkene precursor. In this area we will also look at the possibility of controlling which mirror image of the C-N bond we form. This particular aspect is of relevance in cases where the carbon atom of the C-N bond is attached to three other different groups.Part 2. The second area we will look at is forming C-N bonds in an intermolecular manner. These processes will be much more challenging to develop and we will use the knowledge we gain from Part 1 to aid this aspect.To facilitate these new methods we will examine the chemistry of a specific nitrogenous organic functionality that allows redox neutral C-N bond forming processes; this, in combination with a metal catalyst, will act as the source of nitrogen. The new C-N bond forming reactions will initially be developed in systems where this functionality is part of the same molecule as the alkene with which it reacts. When the new C-N bond forms a ring structure will therefore be generated. As our understanding of the reactions improves, we will see if the organic functionality and alkene can be part of different molecules. This type of C-N bond formation is anticipated to be much more challenging. This research area has been chosen because C-N bonds are vital components in living structures (e.g. amino acids) and drug compounds. By developing these new reactions we will be providing methods which allow chemists to make biologically important molecules in a quicker and more efficient manner. Indeed, these new reactions may even allow people to make molecules which are presently inaccessible. In the long term, this research can benefit wider society by enabling the development of drugs for the treatment of illnesses or by providing molecular probes for understanding biological processes. Additionally, there is an inherent need for new C-N bond forming processes as many current methods are subject to patent protection (e.g. the Buchwald-Hartwig amination) which can limit their deployment in industrial settings.Aspects of this research programme have previously been submitted as part of a successful EPSRC CAF application which was not taken up by the PI as a Royal Society URF was accepted instead.