anti-Carbopalladations of C-C Triple Bonds: Mechanistic Investigations and Starting Point for Novel Domino Reactions

本项目旨在继续关于钯催化的C-C三键反官能化的研究。以前的研究表明，从内部炔烃开始快速有效地获得四取代烯烃。通过实验和计算手段，对反碳加成反应是多米诺骨牌过程的关键进行了机理研究，结果表明，最初关于钯-联烯络合物作为关键中间体的假设是不成立的。密度泛函理论研究和相应的实验表明，在C-C三键的共聚碳配位后，金属配位球内发生了异构化，其先决条件是14价电子络合物的出现有利于单齿和大体积膦配体的形成。有了这个机理知识，已经成功地进行了几个基于反碳分配的多米诺骨牌过程。通过Heck反应和Stille反应终止级联反应，设计并实现了C-H活化或羟基亲核攻击。这些反应(也与天然产物化学)的相关性被正式的LyserGol全合成所证明。作为复杂级联的关键步骤，这些基于反碳分枝的研究应该在下一个资金周期内继续进行。三个工作包将是重点：(I)SP3杂化的碳实体终止序列，(Ii)氧、氮和硫部分终止序列，以及(Iii)在一氧化碳气氛下进行成功的序列引导。第一个工作包旨在用脂肪族硼酸酯进行封端。此外，终止C-H活化的工作将从马利基扩展到环丙基残基。第二个工作包将评估烯醇形式的酮和羧酸盐是否也可能终止级联反应。胺或酰胺对关键的抗碳配位中间体的攻击应为含氮杂环嵌入烯胺单元铺平道路，而亚硫酸盐应导致双键被砜单元取代。第三项工作的重点是一氧化碳的存在是否允许在瀑布上添加羰化步骤的问题。设想的调查还将包括机械实验，如分别对中间体的结晶和捕获。

This project aims to continue the studies regarding the Pd-catalyzedanti-functionalisation of C-C triple bonds. Previous investigations ledto a fast and efficient access to tetrasubstituted alkenes starting frominternal alkynes. Mechanistic investigations (by experimental andcomputational means) of the unusual anti-carbopalladation being thekey of the investigated domino processes revealed that the initialassumption of a Pd-allene complex as crucial intermediate is notvalid. DFT studies and respective experiments demonstrated thatafter the common syn-carbopalladation of the C-C triple bond anisomerization in the coordination sphere of the metal takes place.Prerequisite is the occurrence of a 14-valence electron complex beingfavored by monodentate and bulky phosphine ligands. With thismechanistic knowledge in hand several domino processes based onanti-carbopalladations have successfully been performed. Cascadesbeing terminated via Heck and Stille reactions, C-H activations or thenucleophilic attack of hydroxyl groups have been designed andrealized. The relevance of these reactions (also for natural productchemistry) was demonstrated by a formal total synthesis of Lysergol.These investigations based on anti-carbopalladation as key step ofcomplex cascades should be continued within the next funding period.Three work packages will be in the focus: (i) termination of thesequence by sp3-hybrized carbon entities, (ii) termination by oxygen,nitrogen and sulfur moieties and (iii) conduction of successfulsequences under an atmosphere of carbon monoxide. The first workpackage aims at the termination with aliphatic boronic acid esters. Inaddition, the work on terminating C-H activation will be extended fromaryl to cyclopropyl residues. The second work package will evaluatewhether also ketones in their enol form and carboxylates mightterminate the cascade. An attack of amines or amides to the key anticarbopalladationintermediate should pave the way to nitrogencontainingheterocycles with embedded enamine unit while sulfinatesshould lead to double bonds substituted with sulfone units. The thirdwork package focuses on the question whether the presence ofcarbon monoxide allows adding carbonylation steps to the cascade.The envisioned investigations will also comprise mechanisticexperiments such as crystallization and trapping of respectiveintermediates.