Development of Chiral N-Heterocyclic Photoredox Catalysts for Asymmetric Photo-mediated Synthesis

在传统催化中，催化剂支持催化循环的每一步，并充当反应伴侣。相反，光氧化还原催化剂在许多情况下会引发反应性自由基物种的形成，该物种在没有催化剂缔合的情况下发生反应。然而，过渡金属和有机催化中已知的一些手性诱导机制已经被应用于用光活化底物和控制立体选择性产物的形成。与传统的光氧化还原催化剂不同的是，从嘧啶并四酮类化合物中提取的有机化合物具有双重光氧化还原催化剂和氢原子转移催化剂的作用，并且在没有辅助催化剂或牺牲试剂的情况下可以再生。嘧啶并四酮类黄素结构，但具有较高的激发态氧化还原电位和较高的稳定性。特别是，在乙腈中大于+2.0V的激发态还原电位使多种有机底物的单电子氧化成为可能。以往的研究表明，N取代基的变化对吸收、基态或激发态的电化学性质都没有明显的影响。嘧啶并四酮作为强激发态氧化剂和HAT催化剂的双重作用的确凿证据表明，这两个步骤的立体选择性都可以由单一的手性催化剂控制。因此，基于人工氨基酸和天然氨基酸组成的短肽的手性侧链的实现将导致有效的手性有机光氧化还原催化剂，从而允许立体选择性自由基反应和通过空间和非共价相互作用进行立体专一性氢原子转移。通过量子化学计算的调制，肽和杂环的合成，以及在有机分子构建块的合成中的应用，这三个方面得到了广泛的光谱研究的补充。

In traditional catalysis, the catalyst supports each step of the catalytic cycle and serves as a reaction companion. In contrast, photoredox catalysts in many cases initiate the formation of a reactive radical species that reacts off without catalyst association. However, some of the mechanisms of chiral induction known from transition metal and organocatalysis are already applied for activating substrates with light and controlling stereoselective product formation. Unlike conventional photoredox catalysts that often require the use of a co-catalyst for catalyst recovery, organic from pyrimidopteridine tetraones act as dual photoredox catalysts and hydrogen atom transfer catalysts and can be regenerated in the absence of co-catalysts or sacrificial reagents. Pyrimidopteridine tetraones have a flavin-like structure but exhibit significantly higher excited-state redox potentials and high stability. In particular, the excited-state reduction potential of greater than +2.0 V vs SCE in acetonitriles enables the one-electron oxidation of a wide range of organic substrates. Previous studies showed that neither the absorption nor the ground-state or excited-state electrochemical properties are drastically affected by changes in the N substituents. The solid evidence that pyrimidopteridine tetraones play a dual role as a strong excited-state oxidant and as a HAT catalyst suggests that the stereoselectivity of both steps can be controlled by a single chiral catalyst. Therefore, the implementation of chiral side chains based on short peptides composed of artificial and natural amino acids should lead to potent chiral organic photoredox catalysts that allow both stereoselective radical reaction and stereospecific hydrogen atom transfer through steric and non-covalent interactions. The triad of modulation via quantum chemical calculations, peptide and heterocycle synthesis, and application in the synthesis of organic molecular building blocks is complemented by extensive spectroscopic studies.