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pd催化的C-C三键的反官能化。先前的研究导致了从内炔开始快速有效地获得四取代烯烃。机制研究（通过实验和计算手段）不寻常的抗碳氧化是所研究的多米诺骨牌过程的关键，揭示了Pd-allene复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，在金属配位球中，C-C三键异构化发生共同的同步碳球化后。前提条件是14价电子配合物的出现，有利于单齿和大体积的膦配体。有了这些机械知识在手，几个基于抗碳巴拉的多米诺骨牌工艺已经成功地进行了。级联通过Heck和Stille反应终止，C-H活化或羟基的亲核攻击已经被设计和实现。这些反应的相关性（也适用于天然产物化学）通过Lysergol的正式全合成得到了证明。这些以抗碳巴拉为基础的研究作为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) sp3杂化碳实体终止序列，（ii）氧，氮和硫部分终止序列，（iii）在一氧化碳气氛下成功传导序列。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活化的工作将从环丙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是否也可能终止级联。胺或酰胺对关键的抗碳杂化中间体的攻击将为嵌入烯胺单元的含氮杂环铺平道路，而亚硫酸盐将导致被砜单元取代的双键。第三个工作包关注的问题是一氧化碳的存在是否允许在级联反应中增加羰基化步骤。设想的研究还将包括机械实验，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.