Novel C-C Coupling Reactions under Nickelaphotoredox Catalysis

在有机化学中，催化是一种强有力的策略，它允许高效和经济地合成许多物质。在过去的几年里，光氧化还原催化作为一个新的研究领域得到了广泛的关注，因为它能够在温和的条件下访问非传统的反应场所。具体地说，光氧化还原催化可以利用可见光的能量在光催化剂的存在下将合适的有机底物转化为活性自由基。在本研究项目中，光氧化还原催化的强度应该与镍催化的交叉偶联反应(镍光氧化还原催化)相结合，以构建具有挑战性的C-C键。通过将这两种催化模式结合起来，以前未知或无法到达的机械途径应该被用于复杂分子的快速组装。该项目的第一部分研究开发一种烷基草酸盐与芳基卤化物的脱羧基交叉偶联。草酸盐应该作为稳定的自由基前体发挥作用，在光催化剂存在的情况下，它可以经历两个二氧化碳分子的逐步损失，从而生成以碳为中心的自由基。这些自由基随后可以与芳基卤化物偶联，在镍催化的反应中形成C-C键。这一方法将具有广泛的实用性，因为所需的草酸盐可以很容易地从现成的酒精中获得。该项目的第二部分研究了类似的脱羧基偶联，以实现芳香酯的二氧化碳挤出-重组。在此反应中，镍催化剂应插入芳烃和酯之间的酚类C-O单键。接下来是二氧化碳挤出，这应该由光催化剂来促进。最后，镍催化剂可以进行还原消除，通过新形成的C-C键将两个有机碎片重新结合。由于酯在常见的有机分子中非常普遍，而且可以很容易地从醇和羧酸中合成，因此建议的反应将是普遍感兴趣的。在研究项目的最后部分，应该开发两个所描述的镍光氧化还原反应的不对称版本。能够控制偶联产物的立体化学将大大增加这些反应的价值，因为获得阳离子化合物对生物和医学应用至关重要。为了达到这一目的，需要通过在镍催化剂上引入手性配体来改变反应条件。这种配体将产生一个手性环境，以便中间二有机镍物种的还原消除可以以对映体选择性的方式发生。由于草酸盐交叉偶联和CO2-挤出-复合偶联都是通过类似的二有机镍络合物进行的，因此这一策略应该是普遍适用的。

Catalysis is a powerful strategy in organic chemistry that allows for efficient and economic syntheses of many substances. Over the past few years photoredox catalysis has been established as a new research field, which has gained widespread attention due to its ability to access non-traditional sites of reactivity under mild conditions. Specifically, photoredox catalysis can convert suitable organic substrates into reactive radicals in the presence of a photocatalyst by harnessing the energy of visible light.Within this research project the strength of photoredox catalysis should be merged with nickel-catalyzed cross-coupling reactions (nickelaphotoredox catalysis) to enable the construction of challenging C-C bonds. By combing those two modes of catalysis, previously unknown or inaccessible mechanistic pathways should be utilized for the rapid assembly of complex molecules. The first part of the project investigates the development of a decarboxylative cross-coupling of alkyl oxalates with aryl halides. The oxalate should function as a stable radical precursor, which can undergo a stepwise loss of two molecules of CO2 in the presence of a photocatalyst to generate a carbon-centered radical. Those radicals can subsequently be coupled with aryl halides to form C-C bonds in a nickel-catalyzed reaction. This methodology would be of widespread utility, since the required oxalates could be easily obtained from readily available alcohols.The second part of the project examines a similar decarboxylative coupling to enable a CO2-extrusion-recombination of aryl esters. During this reaction, the nickel catalyst should insert into the phenolic C-O single bond between the arene and the ester. This is followed by CO2-extrusion, which should be facilitated by the photocatalyst. Finally, the nickel catalyst can undergo reductive elimination, which recombines the two organic fragments via a newly formed C-C bond. The proposed reaction would be of general interest, since esters are very prevalent in common organic molecules and can be easily synthesized from alcohols and carboxylic acids.Within the last part of the research project, an asymmetric version of the two described nickelaphotoredox reactions should be developed. Being able to control the stereochemistry of the coupling products would significantly increase the value of those reactions, since having access to enatiopure compounds is crucial for biological and medicinal applications. In order to achieve this, the reaction conditions should be modified by introducing a chiral ligand on the nickel catalyst. This ligand would generate a chiral environment so that the reductive elimination of the intermediate diorganylnickel species could occur in an enantioselective manner. Since the oxalate cross coupling and the CO2-extrusion-recombination coupling both proceed through similar diorganylnickel complexes, this strategy should be universally applicable.