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

交叉偶联反应，其中两个分子被偶联以产生一个新分子，通常被合成化学家用于生产新的候选药物。然而，这些反应不是特别适合于合成手性分子，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显示不同的特性，因此精确控制它们的三维结构在药物发现过程中至关重要。 一个镜像可以充当活性治疗剂，而另一个镜像可能被证明对生物系统有害或可能显著降低活性治疗剂的功效。 Mark Biscoe博士正在研究新的策略和催化剂，以仅产生通过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候选药物的安全性和有效性。Biscoe博士还积极参与旨在增加参与STEM领域学生多样性的项目。 高中生和本科生的暑期研究实习是这些外联活动的重要组成部分。在化学系化学催化计划的资助下，纽约城市学院的Mark Biscoe博士正在探索控制钯催化交叉偶联反应中烷基transmethalo反应性和机理的因素。 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，以deconvolute的影响transmethalo过程的速率和立体化学的因素。 特别关注的是烷基锡（alkylcarbastannatrane）和alkylboron亲核试剂的transmetabolites，最终目标是开发新的，强大的方法，采用光学活性的烷基锡和alkylboron亲核试剂在立体定向交叉偶联反应。这些研究扩展了我们对transmethalo在过渡金属催化反应中涉及烷基偶联伙伴的基本理解，并通过利用这一知识促进了新的立体定向化学转化的发展。 此外，这些活动还包括暑期研究实习，旨在增加STEM领域代表性不足和少数群体的参与。

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.