康龙化成举办第六十二期“合成与药物化学前沿”名师线上讲座
2026年1月29日,北京——美国加州大学尔湾分校化学系Elizabeth R. Jarvo教授受邀做客康龙化成第六十二期“合成与药物化学前沿”名师线上讲座,并作题为“聚焦脂肪醇衍生物的镍催化立体选择性偶联和亲电交叉偶联反应”的学术报告。系统呈现了其团队在合成与药物化学领域的一些创新性研究成果。报告主要介绍了C(sp3)-C(sp3)键的构建,立体专一性环丙烷合成, 1, 3-二磺酸酯的分子内XEC反应,脂肪族磺酸酯的Suzuki-Miyaura交叉偶联等。
Jarvo教授是国际知名的有机合成化学家,长期致力于发展基于镍催化的新型碳-碳键构筑方法,尤其在立体选择性交叉偶联与交叉亲电偶联领域成果卓著。在本次报告中,Jarvo教授系统回顾了其课题组近年来围绕脂肪族醇衍生物(如烷基磺酸酯、卤代物等)在镍催化下的转化策略,并重点介绍了以下几项代表性工作:
C(sp3)-C(sp3)键的构建:镍催化的脂肪族醇衍生物的交叉选择性脱氧甲基化反应。该工作通过巧妙利用NaI促进磺酸酯到碘化物的转化,结合镍催化的自由基XEC机制,解决了脂肪族醇直接甲基化的难题。不仅为“魔力甲基”引入提供了新工具,也为同位素标记药物合成开辟了高效路径,兼具方法学创新性与应用价值。
立体专一性环丙烷合成:Jarvo教授团队发现了一种立体专一性的环收缩反应,可将4-氯代四氢吡喃转化为环丙烷。该转化最初被观察到以氯作为离去基团,随后成功拓展至含烷基氟的底物,展示了C-F键在此类反应中出人意料却切实可行的参与能力。该反应首先在2-(2-萘基)四氢吡喃体系中得以确立,之后进一步扩展至2-乙烯基四氢吡喃,充分体现了该方法的普适性与合成价值。
1, 3-二磺酸酯的分子内XEC反应:针对1,3-二磺酸酯底物,团队开发了镍催化的分子内交叉亲电偶联策略,通过双环化连续过程,高效构建稠合三元/五元碳环体系。机理研究表明,反应涉及烷基碘中间体的原位生成及自由基过程。
脂肪族磺酸酯的Suzuki-Miyaura交叉偶联:展示了镍催化的脂肪族磺酸酯与芳基硼酸的直接偶联,实现了α-芳基谷氨酰亚胺等药物相关骨架的高效构建。该反应不仅兼容杂芳基硼酸,还可通过一锅法从醇出发完成芳基化。机理研究证实生成自由基的过程为立体消融过程;手性双噁唑啉配体在单电子氧化加成的过程起到控制构型的作用,可实现高对映选择性转化。
讲座尾声,Elizabeth R. Jarvo教授与康龙化成的听众就反应机理、底物设计和反应的适用范围等问题展开深入交流,现场讨论热烈。
Frontiers in Synthetic and Medicinal Chemistry
--The 62nd Pharmaron Virtual Lecture
Beijing, China, Jan. 29, 2026—Professor Elizabeth R. Jarvo from the Department of Chemistry at the University of California, Irvine (UC Irvine) was the distinguished speaker for the 62nd "Frontiers in Synthetic & Medicinal Chemistry" online lecture, hosted by Pharmaron. She delivered an academic report titled "Nickel-Catalyzed Stereoselective Cross-Coupling and Cross-Electrophile Coupling Reactions of Aliphatic Alcohol Derivatives," and presented several of her team's innovative research achievements in synthetic and medicinal chemistry. The report primarily covered the construction of C(sp3)-C(sp3) bonds, stereospecific cyclopropane synthesis, intramolecular XEC reactions of 1,3-disulfonates, and Suzuki-Miyaura cross-coupling of aliphatic sulfonates.
Professor Jarvo is an internationally renowned organic chemist who has been dedicated to developing novel nickel-catalyzed methods for constructing carbon-carbon bonds, with outstanding achievements particularly in the fields of stereoselective cross-coupling and cross-electrophile coupling. In this lecture, Professor Jarvo systematically reviewed her group's recent strategies for transforming aliphatic alcohol derivatives (such as alkyl sulfonates, halides, etc.) under nickel catalysis in recent years, and highlighted the following representative work.
C(sp3)-C(sp3) Bond Construction: Nickel-Catalyzed Cross-Selective Deoxygenative Methylation of Aliphatic Alcohol Derivatives. This work ingeniously utilized NaI to promote the conversion of sulfonates to iodides, combined with a nickel-catalyzed radical XEC mechanism, and addressed the challenge of direct methylation of aliphatic alcohols. This research provided a new tool for introducing "magic methyl" groups andopens an efficient pathway for synthesizing isotopically labeled drugs, demonstrating both methodological innovation and practical value.
Stereospecific Cyclopropane Synthesis: Professor Jarvo’s team discovered a stereospecific ring contraction that converts 4-chloro-substituted tetrahydropyrans into cyclopropanes. Initially observed with chloride as the leaving group, this transformation was later successfully extended to substrates bearing alkyl fluorides, demonstrating the unexpected yet viable participation of C–F bonds in this process. The reaction scope was first established using 2-(2-naphthyl)tetrahydropyrans and subsequently broadened to include 2-vinyl-tetrahydropyrans, highlighting the generality and synthetic potential of the method.
Intramolecular XEC Reactions of 1,3-Disulfonates: For 1,3-disulfonate substrates, Professor Jarvo's team developed a nickel-catalyzed intramolecular cross-electrophile coupling strategy thatefficiently constructed fused three-membered/five-membered carbocyclic systems via cascade bicyclization. Mechanistic studies indicated that the reaction involves the in situ generation of alkyl iodide intermediates and radical processes.
Suzuki-Miyaura Cross-Coupling of Aliphatic Sulfonates: The lecture showcased the direct coupling of aliphatic sulfonates with arylboronic acids via nickel catalysis thatenable efficient construction of pharmaceutically relevant skeletons such as α-aryl glutarimides. The reaction is compatible with heteroarylboronic acids and can be performed in a one-pot procedure starting from alcohols. Mechanistic studies confirmed that the radical generation step is stereoablative. Chiral bisoxazoline ligands play a crucial role in stereochemistry control during the single-electron oxidative addition process that enables highly enantioselective transformations.
After the lecture, Professor Jarvo engaged in an in-depth exchange with Pharmaron's audience on topics such as reaction mechanisms, substrate design, and the scope and applicability of the reactions, fostering a lively and enthusiastic discussion.