Photocatalysis for Organic Synthesis

众所周知，无机半导体，如二氧化钛，在合适的底物存在的情况下，在紫外可见光照射下会产生自由基。这个项目将探索这些自由基的化学，特别是识别和优化自由基加成反应，这将是有益于有机合成的。多相光催化有机合成在环境和经济上都很有吸引力，并且有可能实现比传统路线更高的选择性。我们打算探索由已知的羧酸在二氧化钛表面的光-Kolbe反应引发的广泛的自由基加成反应。显示最有希望的反应将被更详细地检查，特别是使用原位EPR光谱(用于观察最初生成的自由基)、原位核磁共振光谱(用于识别中间体和产物)和时间分辨光学光谱(用于观察短寿命物种)来确定反应路径。将对二氧化钛进行初步研究，但我们也将探索通过添加金属来增强空穴：电子分离或氮掺杂以实现可见光激活来改善性能。其他半导体也将尝试可见光激活。该项目的一个关键组成部分是设计和建造反应堆，以将有希望的反应扩大到对制药行业有吸引力的规模。该项目团队在光催化、自由基化学、原位光谱方法和光催化反应器的设计和建造方面拥有丰富的经验。葛兰素史克在选择与制药行业相关的目标反应方面提供建议和帮助。该项目的成功成果可能带来高价值有机合成技术的范式转变。

Inorganic semiconductors such as TiO2 are known to generate free radicals when irradiated with UV-visible light in the presence of suitable substrates. This project will explore the chemistry of such radicals with the particular objective of identifying and optimising free radical addition reactions which will be beneficial in organic synthesis. Organic synthesis driven by heterogeneous photocatalysis is environmentally and economically attractive, and has the potential to achieve higher selectivity to desired products than conventional routes. We propose to explore a wide range of free radical addition reactions initiated by the known photo-Kolbe reaction of carboxylic acids over titania surfaces. Reactions showing the most promise will be examined in more detail, using in particular in-situ EPR spectroscopy (to observe the initially generated free radicals), in-situ NMR spectroscopy (to identify intermediates and products), and time resolved optical spectroscopy (to observe short lived species) to determine the reaction pathways. Initial studies will be made with TiO2, but we will also explore improvements in performance by adding metals to enhance hole:electron separation, or nitrogen dopants to achieve visible light activation. Visible light activation will also be attempted with other semiconductors. A crucial component of the project is the design and construction of reactors for scaling up promising reactions to a scale attractive to the pharmaceutical industry. The project team has wide experience in photocatalysis, free radical chemistry, in-situ spectroscopic methods and photocatalytic reactor design and construction. Advice and assistance in selection of target reactions relevant to the pharmaceutical industry is provided by GlaxoSmithKline. A successful outcome of the project could bring about a paradigm shift in technologies for high value organic synthesis.