转自：康龙化成

康龙化成举办第五十三期“合成与药物化学前沿”名师线上讲座

2025年02月27日，北京—美国威斯康星大学麦迪逊分校Daniel John Weix教授做客康龙化成第五十三期“合成与药物化学前沿”名师线上讲座，报告主题为“交叉亲电偶联中的新型亲电试剂、策略和催化剂”。在讲座中，Weix教授展示了他们在交叉亲电偶联（Cross-ElectrophileCoupling）领域的最新研究成果。Weix教授团队致力于开发新的亲电试剂、策略和催化剂，以推动有机合成中常见亲电试剂的创新应用。

在报告中，Weix教授指出，有机化学对多样化的片段偶联反应有着强烈需求，尤其是在药物研发领域，期望分子具备更多的C(sp³) 特征。传统的反应如酰胺键形成、碳-杂原子键形成以及Suzuki反应已被广泛应用，但仍存在局限性。亲核试剂在合成中存在限制，而交叉亲电体偶联反应为拓展化学空间提供了新途径。尽管这一方法目前发展程度相对较低，但它具有跳过传统R-[M]步骤、避免C-H选择性问题的潜力。

研究人员深入探索了交叉亲电体偶联反应的机理和有机金属化学过程。通过对反应条件的精细调控，包括对配体、还原剂等的筛选，以实现不同亲电体之间的高效偶联。在研究过程中，发现许多常见的亲电体在交叉亲电体偶联反应中存在挑战，例如芳基氯和芳基三氟甲磺酸酯等，它们要么反应活性低，要么会发生不理想的副反应。

针对这些问题，研究人员开发了一系列策略。以卤化物交换为例，它能够提高烷基氯的反应活性；同时，通过对配体的优化，如使用特定的双齿配体PyBCamCN，可以有效平衡反应活性和选择性。在某些情况下，LiCl作为添加剂能够克服三氟甲磺酸酯盐对镍还原的抑制作用，从而促进反应进行。

此外，研究还涉及到一些特殊类型的反应，如受阻C(sp²)-C(sp³)键的形成。这类键在交叉亲电体偶联反应中较为罕见，研究人员尝试利用钴催化来解决镍催化难以实现的反应，取得了一定的成果。同时，对于烷基羧酸作为非自由基亲电体的反应也进行了探索，为获取烷基镍中间体提供了新的思路。

此外，Weix教授还介绍了他们在交叉亲电偶联领域取得的其他进展，包括新型配体设计、多金属催化以及光电化学的应用。这些成果不仅为有机合成提供了新的思路，也为药物研发和材料科学等领域带来了新的机遇。此次报告得到了广泛关注，相关研究成果已发表在《JACS》等国际知名期刊上。Weix教授表示，未来将继续探索交叉亲电偶联的潜力，以实现更多复杂分子的高效合成。

会后，Weix教授在问答环节中与听众进行了热烈的讨论。

Frontiers in Synthetic and Medicinal Chemistry

--The 53rd Pharmaron Virtual Lecture

BeijingChina, February 27, 2025 - Pharmaron held its 53rd virtual lecture in the Frontiersof Synthetic and Medicinal Chemistry series, which was delivered by ProfessorDaniel John Weix from the University of Wisconsin-Madison in the United States. Thetitle of this presentation was "Novel Electrophilic Reagents, Strategies,and Catalysts in Cross-Electrophile Coupling".

Duringthe lecture, the latest research achievements in the field ofcross-electrophile coupling (CEC) by Professor Weix's teamwere presented. Professor Weix's team was committed to developing newelectrophilic reagents, strategies, and catalysts to promote the innovativeapplication of common electrophilic reagents in organic synthesis.

Inthe presentation, Professor Weix pointed out that there was a strong demand fordiverse fragment coupling reactions in organic chemistry, especially in thefield of drug discovery and development, where molecules were expected topossess more C(sp³) characteristics. Traditional reactions such as amide bondformation, carbon-heteroatom bond formation, and Suzuki reaction had beenwidely applied, but they still had limitations. Nucleophilic reagents hadlimitations in synthesis, and the cross-electrophile coupling reaction provideda new approach for expanding the chemical space. Although this method wascurrently at a relatively low level of development, it had the potential toskip the traditional R-[M] step and avoid the C-H selectivity problem.

Themechanism of the cross-electrophile coupling reaction and the organometallicchemical processes were deeply explored by the Prof. Weix’ group. Through thefine-tuning of reaction conditions, including the screening of ligands andreducing agents, the efficient coupling between different electrophiles wasachieved. During the research process, it was found that many commonelectrophiles faced challenges in the cross-electrophile coupling reaction. Forexample, aryl chlorides and aryl trifluoromethanesulfonateseither had low reactivity or would undergo undesirable side reactions.

Toaddress these issues, a series of strategies were developed by Prof. Weix’group. For instance, halide exchange was able to increase the reactivity ofalkyl chlorides. At the same time, through the optimization of ligands, such asthe use of a specific bidentate ligand PyBCamCN, the reactivity and selectivity ofthe reaction could be effectively balanced. In some cases, LiCl, as anadditive, was able to overcome the inhibitory effect of trifluoromethanesulfonatesalts on nickel reduction, thus promoting the reaction.

Inaddition, some special types of reactions were also involved in the research,such as the formation of hindered C(sp²)-C(sp³) bonds. Such bonds wererelatively rare in the cross-electrophile coupling reaction. Prof. Weix’ groupattempted to use cobalt catalysis to solve the reactions that were difficult toachieve with nickel catalysis, and good results were obtained. Meanwhile, thereaction of alkyl carboxylic acids as non-radical electrophiles was alsoexplored, providing new ideas for obtaining alkyl nickel intermediates.

Furthermore,other progresses achieved by Professor Weix's team in the field of cross-electrophilecoupling were also introduced by Professor Weix, including the design of novelligands, multi-metal catalysis, and the application of photoelectrochemistry.These achievements not only provided new ideas for organic synthesis but alsobrought new opportunities to fields such as drug discovery and development andmaterial science. This lecture received widespread attention, and the relatedresearch results had been published in internationally renowned journals suchas . Professor Weix stated thatthe potential of cross-electrophile coupling would be continuously explored inthe future to achieve the efficient synthesis of more complex molecules.

Afterthe meeting, a lively discussion was carried out by Professor Weix with theaudience during the Q&A session.

（转自：康龙化成）