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

钯催化交叉偶联反应中烷基转移金属化的反应活性及机理探讨

基本信息

批准号：
1665189
负责人：
Mark Biscoe
金额：
$ 41.42万
依托单位：
CUNY City College
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1665189&HistoricalAwards=false
关键词：
Probing Reactivity Mechanism Alkyl Transmetallation

项目摘要

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.

交叉偶联反应，即两个分子偶联产生一个新分子，是合成化学家在努力生产新的候选药物时经常使用的方法。然而，这些反应并不特别适合于手性分子的合成，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显示出不同的特性，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。一个镜像可以作为活性治疗剂，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镜像的功效。马克·比斯科博士正在研究新的策略和催化剂，以产生由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的候选药物的安全性和有效性。Biscoe博士还积极参与旨在增加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拓展活动的重要组成部分。在化学部化学催化项目的资助下，纽约城市学院的Mark Biscoe博士正在探索控制钯催化的交叉偶联反应中烷基金属转化反应活性和机理的因素。这些研究结合了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计算来解开影响金属转化过程速率和立体化学的因素。重点放在烷基锡（烷基卡丁烷）和烷基硼亲核试剂的金属转化上，最终目标是开发新的、强大的方法来利用光学活性烷基锡和烷基硼亲核试剂进行立体特异性交叉偶联反应。这些研究扩展了我们对涉及烷基偶联伙伴的过渡金属催化反应中的金属转化的基本理解，并通过利用这些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，旨在提高代表性不足和少数群体在STEM领域的参与度。