Probing Reactivity and Mechanism of Alkyl Transmetallation in Palladium-Catalyzed Cross-Coupling Reactions

交叉偶联反应，即两个分子连接起来产生一个新的分子，通常被合成化学家用来努力生产新的候选药物。然而，这些反应并不是特别适合手性分子的合成，例如，具有三维结构的分子可以作为不可重叠的镜像存在，类似于你的右手和左手。由于这些不同的镜像通常表现出不同的属性，因此在药物发现过程中，精确控制它们的三维结构是必不可少的。一个镜像可能充当主动治疗剂，而另一个镜像可能证明对生物系统有害或可能显著降低主动镜像的疗效。马克·比斯科博士正在研究新的策略和催化剂，以仅产生交叉偶联反应产生的分子的所需镜像结构。这项工作有助于提高新药候选药物的安全性和有效性。比斯科博士还积极参与旨在增加参与STEM领域的学生多样性的项目。针对高中生和本科生的暑期研究实习是这些外展活动的重要组成部分。在化学系化学催化项目的资助下，纽约城市学院的Mark Biscoe博士正在探索在钯催化的交叉偶联反应中控制烷基转移金属反应活性的因素和机理。这些研究利用催化和化学计量过程、立体化学探针、现代数据分析技术和DFT计算的组合来解开影响跨金属转移过程的速度和立体化学的因素。特别关注烷基锡(烷基碳氮杂环丁烷)和烷基硼亲核试剂的跨金属反应，最终目标是开发新的、强有力的方法，在立体定向交叉偶联反应中使用光学活性的烷基锡和烷基硼亲核试剂。这些研究扩展了我们对过渡金属催化的烷基偶联反应中跨金属反应的基本理解，并通过利用这些知识促进了新的、立体特异的化学转化的发展。此外，这些活动包括暑期研究实习，旨在增加代表不足的群体和少数群体在科技、经济和经济领域的参与。

Cross-coupling reactions, where two molecules are coupled to produce a new molecule, are routinely employed by synthetic chemists in efforts to produce new drug candidates. However, these reactions are not especially well-suited for the synthesis of chiral molecules, e.g., molecules with three-dimensional structures that can exist as non-superimposable mirror images, similar to your right and left hands. Because these different mirror images usually display distinct properties, precise control of their three-dimensional structure is essential in the drug discovery process. One mirror image may serve as the active therapeutic agent, while the other may prove harmful to biological systems or may significantly reduce the efficacy of the active one. Dr. Mark Biscoe is investigating new strategies and catalysts to produce only the desired mirror image structure of molecules produced by cross-coupling reactions. This work is contributing to the improved safety and efficacy of new drug candidates. Dr. Biscoe is also active in projects that are designed to increase the diversity of students participating in the STEM fields. Summer research internships for high school and undergraduate students constitute an important part of these outreach activities. With funding from the Chemical Catalysis Program of the Chemistry Division, Dr. Mark Biscoe of the City College of New York is exploring the factors that control the reactivity and mechanism of alkyl transmetallation in palladium-catalyzed cross-coupling reactions. These studies utilize a combination of catalytic and stoichiometric processes, stereochemical probes, modern data analysis techniques, and DFT calculations to deconvolute the factors that influence the rate and stereochemistry of the transmetallation process. Particular focus is placed on the transmetallation of alkyltin (alkylcarbastannatrane) and alkylboron nucleophiles, with the ultimate goal of developing new, robust methods to employ optically active alkyltin and alkylboron nucleophiles in stereospecific cross-coupling reactions. These studies expand our fundamental understanding of transmetallation in transition metal-catalyzed reactions involving alkyl coupling partners, and facilitate the development of new, stereospecific chemical transformations through the exploitation of this knowledge. Additionally, these activities include summer research internships designed to increase the participation of underrepresented and minority groups in STEM fields.