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

本项目旨在继续开展Pd催化C-C三键反功能化的研究。先前的研究导致从内部炔烃开始快速有效地获得四取代烯烃。对作为所研究的多米诺骨牌过程的关键的不寻常的反碳钯化的机理研究（通过实验和计算手段）表明，Pd-丙二烯络合物作为关键中间体的最初假设是无效的。 DFT研究和相关实验表明，C-C三键的共同顺式碳钯化后，金属配位层中会发生异构化。前提是形成单齿大体积膦配体有利于的14价电子配合物。有了这些机械知识，已经成功地执行了几个基于反卡波钯的多米诺骨牌过程。通过 Heck 和 Stille 反应、C-H 激活或羟基的亲核攻击终止级联已被设计和实现。这些反应（也适用于天然产物化学）的相关性通过麦角醇的正式全合成得到了证明。这些基于抗碳钯化作为复杂级联关键步骤的研究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杂化碳实体终止序列，（ii）通过氧、氮和硫部分终止，以及（iii）在碳气氛下成功进行序列一氧化碳。第一个工作包旨在用脂肪族硼酸酯进行终止。此外，终止C-H活化的工作将从芳基残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。胺或酰胺对关键的抗碳钯化中间体的攻击应为具有嵌入烯胺单元的含氮杂环铺平道路，而亚磺酸盐应导致双键被砜单元取代。第三个工作包重点关注一氧化碳的存在是否允许在级联中添加羰基化步骤的问题。设想的研究还将包括机械实验，例如各自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.