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

本项目旨在继续研究钯催化的碳-碳三键的反功能化反应。以前的研究导致了一个快速和有效的获得四取代烯烃从中间体炔。通过实验和计算手段对不寻常的反碳钯化反应的机理进行了研究，发现钯-联烯络合物作为关键中间体的最初假设是不成立的。DFT研究和相应的实验表明，在C-C三键的顺式碳钯化后，金属配位层发生了异构化反应，其前提是在单齿和大体积膦配体的作用下，形成14价电子络合物。有了这方面的机械知识，几个基于抗碳钯化的多米诺骨牌过程已经成功地进行了。通过Heck和Stille反应、C-H活化或羟基亲核攻击终止级联反应已被设计和实现。这些反应的相关性（也用于天然产物化学）通过麦角醇的正式全合成得到证实。这些基于反碳钯化的研究是复杂级联的关键步骤，应在下一个资助期内继续进行。三个工作包将成为重点：（i）通过sp3-杂化碳实体终止这些序列，（ii）通过氧终止，氮和硫部分和（iii）在一氧化碳气氛下的成功序列的传导。第一个工作包的目的是终止与脂肪族硼酸酯。此外，终止C-H活化的工作将从酰基扩展到环丙基残基。第二个工作包将评估是否也酮在他们的烯醇形式和羧酸可能终止级联。胺或酰胺对关键的抗碳钯中间体的攻击将为嵌入烯胺单元的含氮杂环化合物铺平道路，而亚磺酸酯将导致被砜单元取代的双键。第三个工作包的重点是一氧化碳的存在是否允许增加羰基化步骤的级联的问题。设想的调查也将包括机械实验，如结晶和捕获各自的中间体。

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.