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

开发用于构建全碳四元立构中心的催化对映选择性方法：烷基-、乙烯基-和炔基硼亲核试剂与α、β-不饱和亲电子试剂的不对称钯催化共轭加成

• 批准号: 318856427
• 负责人: Dr. Denis Kröger
• 金额: --
• 依托单位: Division of Chemistry and Chemical Engineering
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/318856427?language=en
• 关键词: Development; Catalytic; Enantioselective; Method; Construction

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.

全碳四元立体中心的对映选择性结构（附着四个不同的碳取代基的碳原子）对于各种研究领域都具有重大兴趣。由于其三维性，未充满膨胀的化学空间大大增加了。与之相关的是，将提供新的机会，在广泛使用的扁平分子的情况下，这将无法提供。尽管如此，只有少数营业额最高的药物具有全碳四元立体中心。这些立体中心都没有通过化学合成来构建。在所有情况下，这些结构均来自天然产品。基于这种情况，可以获得两个主要见解。一方面，这种手性分子的潜力在很大程度上是没有被倍增的，另一方面，由于其积累，缺乏广泛适用的合成策略。因此，研究项目的目的是在易于可行的合成条件下和原子经济方式开发和建立一种通用方法，以建造这些类型的立体中心。受钯催化的不对称结合物添加芳基硼酸在β-取代的环状烯酮中添加的启发，该循环烯烃仅限于芳基硼龙亲核试剂，将接受该研究项目。这种新方法旨在克服到目前为止的局限性，并允许实施众多取代基。该项目应通过使用新的钯基催化剂和稳定的烷基烷基，乙烯基和5nnylboron核醇和功能化的侧甲素以及稳定的烷基，乙烯基和烷基烷基核酸酯以及功能化的Sidechains来实现。特别是由于将硼核试剂与功能化的侧技术（例如氨基酸或异芳基化合物）使用的机会，所提出的方法将与以前的方法强烈对比，并还可以为进一步的多面反应提供可能性。