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.

合成化学家通常使用两个分子耦合以产生新分子的交叉偶联反应，以生产新药物。但是，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，可以作为不可感染的镜像图像，类似于您的右手和左手。由于这些不同的镜像通常显示出不同的属性，因此在药物发现过程中，精确控制其三维结构至关重要。一个镜像可以用作活性治疗剂，而另一个镜像可能对生物系统有害，或者可能会显着降低活性剂的功效。马克·比斯科（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图像结构。这项工作有助于提高候选药物的安全性和功效。 Biscoe博士还活跃于旨在增加参与STEM领域的学生多样性的项目。高中和本科生的夏季研究实习构成了这些外展活动的重要组成部分。借助化学级化学催化计划的资金，纽约市城市学院的马克·比斯科（Mark Biscoe）博士正在探索控制钯催化的交叉偶联反应中烷基反应性的反应性和机制的因素。这些研究利用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计算的结合，以反应影响跨金属过程的速率和立体化学的因素。特别关注烷基蛋白（烷基钙化烷）和烷基硼龙亲核试剂的透射率，其最终目的是开发新的，可靠的方法在立体的交叉偶联反应中采用光学活跃的烷基丁素和烷基核核酸盐核酚。这些研究扩展了我们对涉及烷基偶联伴侣的过渡金属催化反应中的跨金属的基本理解，并通过利用这种知识来促进新的立体特异性化学转化。此外，这些活动包括夏季研究实习，旨在增加代表性不足和少数群体在STEM领域的参与。