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

双光氧化还原/过渡金属催化开发新型不对称烯丙基化反应

• 批准号: 508111715
• 负责人: Professor Dr. Bernhard Breit
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/508111715?language=en
• 关键词: Development; novel; asymmetric; allylation; reactions

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.

烯丙基化反应是有机化学中最重要的反应之一。烯丙基化合物在合成上用途广泛，并且在各种天然产物中普遍存在。标准的烯丙基化方法如烯丙基取代、烯丙基氧化、联烯、炔和1，3-二烯的加氢官能化以及烯丙基金属物质与羰基/亚胺的加成反应通常在适用性方面受到限制。特别是引入形式上“硬”的亲核试剂通常是困难的。随着光氧化还原催化作用的建立，C，C键形成化学的机理发生了从普通的双电子到单电子过程的变化。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的组合（双催化）是这方面的主要驱动力。除了很少的文献例子，立体分散的双重光氧化还原-/过渡金属催化剂几乎是未知的。完全未知的是立体分散协同过渡金属催化剂，其中一种金属催化剂另外起到光催化剂的作用。在博士项目的框架内，这种方法应详细说明对氨基酸的不对称合成。在具体的，光诱导，双钯/铜催化的甘氨酸酯的烯丙基化计划。可去除的金属导向基团应有助于基材结合到光催化活性铜催化剂上和随后的自由基形成。平行地，钯催化剂应活化烯丙基亲电试剂，并与铜催化剂一起使得能够形成C，C-键。本项目的重点在于建立立体分散催化条件，第二个项目是将“硬”亲核试剂应用于烯丙基化反应，通过铑和铑的组合催化。因此，光催化产生的酰基自由基与铑烯丙基络合物的烯丙基化是有计划的。除了直接形成酰基自由基外，还应研究其在CO掺入后的间接形成。联烯和炔在该反应中应作为烯丙基前体。使用1，1-二取代的联烯应该能够构建手性季碳原子。最后，应证明制造重要合成构件的方法的价值，这两个项目都包括更好地理解反应过程的机理研究。除此之外，所开发的方法的综合可行性应通过详细阐述全面的基质范围来证明。