Synthetic Photochemistry of Carbanion Equivalents

许多锂化合物的合成光化学还没有被研究和发现。以前在Clayden基团中，人们意识到锂化的苯甲酰胺可以经历电环闭合来脱芳香化芳环，得到共轭的烯酸锂。然后，这种烯酸酯经历了一系列的光化学转化，得到了由手性或非手性苯基苯甲酰胺形成的环庚三烯底物，考虑到使用了过于简单的试剂，这是一个相当惊人的转变。然而，这项工作暂停了，因为效率低下的钨灯照射了许多不需要的热量，这会降解敏感的锂化烯醇类中间体。现代LED效率更高，价格也更实惠，而且不会产生这种不必要的热辐射。因此，该小组已经表明，这种化学可以在高产率和高对映体选择性(存在手性中心的情况下)进行。现在，我们想要询问这个过程，中间体的反应活性和最终产品形成的机理途径。最初，这将包括尝试测量活性烯醇酸锂的紫外线光谱，以确定它们在电磁光谱中的吸收位置。然后，我们将致力于最大化到达中间体的光强度，以及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材料在其光化学转化方面可能是独一无二的，方法是测量相关(可能是非手性的或具有有限共轭的)酰胺的UV光谱，并在试图使用特定波长的灯强制这些物种的光化学转化之前观察它们吸收的波长。我们希望这可以通过允许与苯甲酰胺有很大不同的大量共轭体系的光化学反应来极大地扩大这些转化的范围。如果不能从相关的起始酰胺中启动类似的化学，可以使用计算方法或可视化(如使用虚拟现实，VR)来进行分子轨道的研究。由于光化学转换被认为是性质上的周环，相关的酰胺可以被检查以确定当与我们已知的反应相比时，它们所需的重叠的分子轨道是如何不同的。这一计算观点可以提供有趣的数据，说明在允许光化学转化的锂化合物中发生了哪些光化学激发。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，并试图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。这最终将引导我们利用我们的化学来应用于合成挑战药物分子，从而在工业上提供潜在的(和合成上简单的)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，从简单的起始材料到更大的合成环只需一到两步。这个项目的新颖性源于目前对锂化苯甲酰胺的光化学研究的缺乏，以及仅使用商业LED作为引发剂就可以轻松合成复杂结构的可能性。该项目旨在成为以实验室为基础的合成化学与技术整合(如光化学、流动和虚拟现实)的集体组合。特别是流动化学可以提供一种在短时间内获得大量最终产品的有效方法，前提是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.