Development of a Catalytic Enantioselective Method for the Construction of All-Carbon Quaternary Stereocenters: The Asymmetric Palladium-Catalyzed Conjugate Addition of Alkyl-, Vinyl-, and Alkynylboron Nucleophiles to alpha, beta-Unsaturated Electrophiles

全碳季立体中心（四个不同的碳取代基连接的碳原子）的对映选择性结构是各个研究领域的重要兴趣。由于其三维性，未开发的化学空间大大增加。与此相关，新的机会将提供，这是不可用的情况下，广泛使用的非手性扁平分子。尽管如此，只有少数具有最高周转率的药物具有全碳季立体中心。这些立体中心都不是化学合成的。在所有情况下，这些结构都来源于天然产物。基于这种情况，可以获得两个主要的见解。一方面，这种手性分子的潜力在很大程度上没有得到充分的开发，另一方面，缺乏广泛适用的合成策略来构建它。因此，研究项目的目标是发展和建立一种通用的方法，在容易实现的合成条件下，以原子经济的方式构建这些类型的立体中心。受钯催化的芳基硼酸对β取代环烯酮的不对称共轭加成的启发，该研究项目将被采用。这种新方法旨在克服迄今为止的局限性，并将允许实现许多取代基。该项目将通过使用含有双或三齿n -杂环碳（NHC）配体的新型钯基催化剂以及具有官能化侧链的稳定的烷基、乙烯基和烷基硼亲核试剂来实现。特别是由于有机会使用具有功能化侧链的硼亲核试剂（例如氨基酸或杂芳烃化合物），所提出的方法将与以前的方法形成强烈对比，并将进一步提供多方面反应的可能性。

The enantioselective construction of all-carbon quaternary stereocenters (carbon atoms to which four distinct carbon substituents are attached) is of significant interest for various fields of research. Due to its three-dimensionality, the underexplored chemical space is increased substantially. Associated therewith, new opportunities will be offered, which are not available in the case of broadly used achiral flat molecules. In spite of that, only a few of the drugs with the highest turnover have all-carbon quaternary stereocenters. None of these stereocenters have been constructed by chemical synthesis. In all cases, those structures are derived from natural products. Based on this situation, two main insights can be gained. On the one hand, the potential of such chiral molecules is largely underexplored, and on the other hand, there is a lack of broadly applicable synthetic strategies for its build-up. Thus, the objective of the research project is to develop and to establish a universal method for the construction of these kinds of stereocenters under easily practicable synthetic conditions and in an atom-economical manner. Inspired by a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to beta-substituted cyclic enones, which is limited to arylboron nucleophiles, the research project will be taken up. This new method aims to overcome the limitations so far and will allow the implementation of numerous substituents. The project shall be realized by the use of new palladium based catalysts containing bi- or tridentate N-heterocyclic carbene (NHC) ligands together with stable alkyl, vinyl and alkynylboron nucleophiles with functionalized sidechains. Particularly due to the opportunity of using boron nucleophiles with functionalized sidechains (e.g. amino acids or heteroaromatic compounds), the proposed method will strongly contrast to former methods and will additionally provide the possibility for further multi-faceted reactions.