Development of novel asymmetric allylation reactions by dual photoredox-/transition metal catalysis

烯丙化反应是有机化学中最重要的转化反应之一。烯丙基化合物的合成用途广泛，在各种天然产物中普遍存在亚结构。标准的烯丙基化方法，如烯丙基取代、烯丙基氧化、烯丙烯、炔和1,3-二烯的加成反应以及烯丙基金属与羰基/亚胺的加成反应等，在适用性方面往往存在局限性。特别是引入正式的“硬”亲核试剂往往是困难的。随着光氧化还原催化的建立，C、C键形成化学发生了由普通的双电子过程到单电子过程的机理变化。这大大简化了对一些以前具有挑战性的分子模式的访问。光氧化还原催化和过渡金属催化（双催化）的结合是这方面的主要推动力。除了少数文献例子外，立体发散双光氧化还原/过渡金属催化剂几乎不为人所知。完全未知的是立体发散的协同过渡金属催化剂，其中一种金属催化剂还起到光催化剂的作用。在博士项目的框架内，应该详细阐述这种方法对氨基酸的不对称合成。在混凝土中，光诱导的双钯/铜催化的甘氨酸酯烯丙基化被计划。可移动的金属导向基团应促进底物与光催化活性铜催化剂的结合和随后的自由基形成。同时，钯催化剂应激活烯丙基亲电试剂，并与铜催化剂一起使C，C键形成。本项目的主要重点在于建立立体发散催化条件。在第二个项目中，“硬”亲核试剂应应用于光催化和铑催化相结合的烯丙基化反应。因此，计划将光催化生成的酰基自由基与铑-烯丙基配合物进行烯丙化。除了直接形成酰基自由基外，还应研究CO掺入后酰基自由基的间接形成。在这个反应中，烯和炔应该作为烯丙基前体。使用1,1-二取代的烯应该能够构建手性季碳原子。最后，该方法的价值，为制造重要的合成构件应该证明。这两个项目都包括机理研究，以便更好地了解反应过程。除此之外，应通过制定一个全面的底物范围来证明所发展的方法的综合可行性。

Allylation reactions are among the most important transformations in organic chemistry. Allylic compounds are synthetically versatile in use and ubiquitous substructures in various natural products. The standard allylation methods like allylic substitution, allylic oxidation, hydrofunctionalization of allenes, alkynes and 1,3-dienes and addition reactions of allyl-metal species to carbonyls/imines often suffer from limitations in terms of applicability. Especially the introduction of formally “hard” nucleophiles is often difficult. Together with the establishment of photoredox catalysis a mechanistic change in C,C-bond formation chemistry from common two-electron to one-electron processes happened. This simplified the access to some previously challenging molecular patterns significantly. The combination of photoredox catalysis and transition metal catalysis (dual catalysis) was a major driving force in this context. Apart from few literature examples, stereodivergent dual photoredox-/transition metal catalyses are hardly known. Completely unknown are stereodivergent synergistic transition metal catalyses where one of the metal catalysts is additionally taking the role of a photocatalyst. Within the framework of a PhD project this approach should be elaborated towards an asymmetric synthesis for amino acids. In concrete, the light-induced, dual palladium-/copper-catalyzed Allylation of glycine esters is planned. A removable metal- directing group shall facilitate substrate binding to a photocatalytically active copper catalyst and subsequent radical formation. In parallel, the palladium catalyst should activate an allylic electrophile and together with the copper catalyst enable the C,C-bond formation. The main focus of this project lies in the establishment of stereodivergent catalytic conditions.In a second project, “hard” nucleophiles should be applied in allylation reactions by combination of photocatalysis and rhodium catalysis. Therefore, the allylation of photocatalytically generated acyl radicals with rhodium-allyl complexes is planned. Next to the direct formation of acyl radicals, their indirect formation after CO incorporation should be investigated. Allenes and Alkynes should serve as allylic precursors in this reaction. The use of 1,1-disubstituted allenes should enable the construction of chiral quaternary carbon atoms. Finally, the value of the methodology for the fabrication of important synthetic building blocks should be demonstrated.Both projects include mechanistic studies for a better understanding of the reaction process. Apart from that, the synthetic viability of the developed methods should be demonstrated by elaboration of a comprehensive substrate-scope.