Re-Inventing Olefin Oxidation Using Visible-Light Photocatalysis

烯烃是从石油和植物生物质中容易获得的原料，在制备高价值材料中起着不可或缺的作用。特别是，氧化反应用于在烯烃碳上引入氧原子，从而将这些分子转化为广泛的合成中间体，如醛、酮、醇和羧酸。烯烃氧化通常使用臭氧分解反应进行，该反应主要用于大宗化学工业，在那里可以对结构简单的材料进行安全和大规模的工艺。精细化工部门(制药和农化工业)不使用这种反应性，因为它们的底物很复杂，含有脆弱的官能团。这意味着，仍需要采取多步骤的方法来克服这一综合挑战。发明一种新的化学策略，能够实现烯烃积木的全面和选择性氧化，对于促进和简化对我们社会至关重要的分子的识别和制备具有重要的战略意义。这项提议的总体目标是开发第一个能够使烯烃积木的氧化裂解生成醛和酮的可见光介导光化学反应的例子。通过这种方式，我们将提供一种独特的反应，能够简化目前难以制备但受到制药和农用化学品发现计划追捧的含氧片段的合成。-我们的目标是使用简单的硝基芳烃，这是一种每年生产数吨规模的大类原料，作为光活性氧化剂，与可见光和光催化剂相结合。这一策略将探索硝基芳烃通过直接能量转移经历光激发到其三重态的能力。然后，这些物种将与烯烃进行新颖的自由基[3，2]型环加成反应，得到一类新的杂环。这个反应形成的物种可以有效地被认为是N掺杂的臭氧化合物，并将在C-C键上发生快速裂解，从而导致氧化材料。-我们将进行详细的机理研究，以充分了解三硝基芳烃的活化过程和反应性。-然后，我们将以这种反应为基准，实现逐渐复杂和功能化的烯烃的氧化。我们的目标是准备一个大型的硝基芳香族化合物库来评估继承人的三重态反应性。这可能使能够根据空间或电子因素选择性地区分烯烃的试剂的鉴定成为可能。总体而言，该项目将为烯烃的快速、选择性和温和氧化制定一项创新战略。获得这些高价值材料的可能性将促进治疗剂和农用化学品的发现、开发和制造，对英国社会的福祉产生全面影响。

Olefins are feedstocks readily available from petroleum and vegetable biomass with an integral role in the preparation of high-value materials. In particular, oxidation reactions are used to introduce oxygen atoms across the olefin carbons and thus convert these molecules into a broad spectrum of synthetic intermediates like aldehydes, ketones, alcohols and carboxylic acids.Olefin oxidation is generally performed using the ozonolysis reaction which is mostly adopted by the bulk chemical industry where safe and large-scale processes on structurally simple materials are possible. The fine chemical sector (pharmaceutical and agrochemical industries) do not use this reactivity as their substrates are complex and contain fragile functionalities. This means that multi-step approaches are still required to overcome this synthetic challenge. The invention of a new chemical strategy able to achieve the general and selective oxidation of olefin building blocks is of strategic importance to facilitate and streamline the identification and the preparation of molecules critical to our society.The overarching aim of this proposal is to develop the first example of a visible-light-mediated photochemical reaction enabling the oxidative cleavage of olefin building blocks to produce aldehydes and ketones. In this way, we will provide a unique reaction able to streamline the synthesis O-containing fragments currently difficult to prepare but highly sought after by pharmaceutical and agrochemical discovery programs.- We aim to use simple nitro-aromatics, a large class of feedstocks produced annually on multi ton-scale, as photoactive oxidants in combination with visible-light and a photocatalyst. This strategy will explore the ability of nitro-arenes to undergo photoexcitation to their triplet state by direct energy-transfer. These species will then engage in novel radical [3+2]-type cycloadditions with olefins to give a new class of heterocycles. The species formed by this reaction can be effectively considered as N-doped ozonides and will undergo fast cleavage across the C-C bond thus leading to the oxidised materials.- We will run detailed mechanistic studies to fully understand the activation process as well as the reactivity of triple nitro-arenes.- We will then benchmarke this reactivity to achieve the oxidation of progressively more complex and functionalised olefin building blocks. We aim to prepare a large library of nitro-aromatics to evaluate heir triplet state reactivity. This might enable the identification of reagents able to selectively discriminate between olefins based on steric or electronic factors. Overall, this project will develop an innovative strategy for the fast, selective and mild oxidation of olefins. The possibility to access these high-value materials will facilitate the discovery, development and manufacture of therapeutic agents and agrochemicals with overall impact to the well-being of UK society.