Synthetic Photochemistry of Carbanion Equivalents

许多锂化物质的合成光化学尚未被研究和发现。以前在Clayden组中，人们认识到锂化苯甲酰胺可以进行电环闭环以使芳环脱芳构化，得到共轭的烯醇化锂。然后，这种烯醇化物经历了一系列的光化学转化，这使得从手性或非手性苄基苯甲酰胺整体形成环庚三烯底物，考虑到使用简单化试剂，这是相当惊人的转化。然而，这项工作被停止，因为效率低下的钨丝灯辐射了许多不必要的热量，这降解了敏感的锂化烯醇化物中间体。现代LED更高效，更实惠，不会产生这种不必要的热辐射。因此，该小组已经表明，这种化学反应可以以良好的产率和高对映选择性（其中存在手性中心）进行。现在，我们想询问这个过程，中间体的反应性和最终产物形成的机制途径。最初，这将涉及尝试测量反应性烯醇化锂的紫外光谱，以确定它们在电磁光谱中吸收的位置。然后，我们的目标是最大限度地提高到达中间体的光强度，并优化发射到混合物上的光波长。然后，我们有能力调查为什么我们的苯甲酰胺起始物料在其光化学转化中可能是独特的，通过测量相关（可能是非手性或有限共轭）酰胺的紫外光谱，并观察它们吸收的波长，然后尝试通过使用特定波长的灯强制这些物质的光化学转化。我们希望这可以大大拓宽这些转换的范围，通过允许大量的共轭系统，从苯甲酰胺有很大的不同的光化学反应。如果类似的化学反应不能从相关的起始酰胺开始，则可以使用计算方法或可视化（例如使用虚拟现实，VR）对分子轨道进行可能的研究。由于光化学转化被认为是周环的性质，相关的酰胺可以进行检查，以确定它们的分子轨道如何不同所需的重叠时，我们已知的反应相比。这种计算的观点可以提供有趣的数据，光化学激发发生在锂化烯醇化物，允许光化学转化。我们的目标也是通过尝试捕获可能的中间体（例如通过自由基捕获途径）来研究这些转化的可能机制，并尝试通过分离光化学途径中的关键中间体来排除可能的周环途径。这将最终导致我们利用我们的化学应用于合成具有挑战性的药物分子，在工业中提供潜在的（和合成简单的）应用。考虑到目前围绕光化学形成的广泛兴趣，这一过程有可能简化许多途径，以一个或两个步骤从简单的起始材料合成更大的环。该项目的新奇源于目前缺乏对锂化苯甲酰胺光化学的研究，以及仅使用商业LED作为引发剂轻松合成复杂结构的潜力。该项目旨在将基于合成实验室的化学与技术简化（如光化学，流动和VR）相结合。流动化学特别地可以提供在短时间内获得大量最终产品的有效方法，假设可以实现对流动装置的温度控制。

The synthetic photochemistry of many lithiated species is unresearched and undiscovered. Previously in the Clayden group, it was realised that lithiated benzamides may undergo an electrocyclic ring-closing to dearomatize an aromatic ring, giving a conjugated lithium enolate. This enolate then underwent a series of photochemical transformations which gave an overall formation of a cycloheptatriene substrate from a chiral or achiral benzyl benzamide, which is a rather striking transformation considering the use of the simplistic reagents. However, this work was halted since the inefficient tungsten lamps irradiated much unwanted heat, which degraded the sensitive lithiated enolate intermediates. Modern LEDs are much more efficient and affordable and do not produce this unwanted heat radiation. As a result, the group has shown this chemistry can be carried out in good yields and high enantioselectivity (where a chiral centre is present). Now, we want to interrogate this process, the reactivity of intermediates and the mechanistic pathway for the final product formation. Initially this will involve attempting to measure the UV-spectra of the reactive lithium enolates to identify where they absorb in the electromagnetic spectrum. We then will aim to maximise the light intensity reaching the intermediates as well as optimising the light wavelength emitted onto the mixture. We then have the ability to investigate why our benzamide starting materials are potentially unique in their photochemical transformations, by measuring UV-spectra of related (perhaps achiral or with limited conjugation) amides and observing what wavelength they absorb before attempting to force photochemical transformations of these species by using lamps of specific wavelengths. We hope this can vastly widen the scope for these transformations by allowing the photochemical reaction of a multitude of conjugated systems that differ widely from benzamides. If similar chemistry cannot be initiated from related starting amides, a possible study on molecular orbitals could be carried out using computational methods or visualisation (such as using virtual reality, VR). Since the photochemical transformations are thought to be pericyclic in nature, the related amides could be examined to identify how their molecular orbitals differ for the required overlap when compared to our known reactions. This computational view could provide interesting data about which photochemical excitations are occurring within the lithiated enolates which allows the photochemical transformations. We would aim to also investigate the possible mechanisms for these transformations by attempting to trap possible intermediates (such as through a radical-trapping pathway) and attempt to rule out possible pericyclic pathways where possible by isolating key intermediates in the photochemical pathway. This would eventually lead us to utilise our chemistry in application to synthetically challenging pharmaceutical molecules, giving potential (and synthetically simple) application in industry. Considering the wide interest currently forming around photochemistry, this process has the potential to simplify many pathways to larger synthetic rings from simple starting materials in one or two steps. The novelty of this project arises from the lack of current research on the photochemistry of lithiated benzamides and the potential for facile synthesis of complex structures using just commercial LEDs as the initiator. This project aims to be a collective mix of synthetic lab-based chemistry with technology incorporations (such as photochemistry, flow and VR). Flow chemistry in particular may provide an efficient approach to obtaining a large amount of final product in a short space of time, assuming temperature control on the flow apparatus can be achieved.