New Approaches to Stereospecific Alkyl Transfer in Metal-Catalyzed Reactions: Synthetic and Mechanistic Investigations

美国国家科学基金会化学部的化学合成计划通过该奖项支持Biscoe教授的研究，他的实验室开发了用于有机化学和药物化学的新合成策略。两种成分和结构相同但互为镜像的分子可以引起截然不同的生物反应。因此，能够精确控制三维分子结构的合成方法是必不可少的。金属催化的交叉偶联反应通常被药物化学家用于生产具有生物活性的化合物。然而，这些反应对于平面分子单元的制备是最可靠的，而对于三维分支分子结构的制备则不可靠。比斯科教授的研究探讨了制备分支分子单独镜像的新策略。从这些研究中，新的化学反应被开发出来，加速了手性分子的合成，并有助于提高药物和其他生物相关化合物在发现过程中的安全性和有效性。Biscoe博士积极参与旨在增加STEM领域学生多样性的项目。作为这些外展活动的一部分，Biscoe博士发起了CCNY和城市学院数学，科学和工程高中（HSMSE）之间的联合研究计划。该项目的目标是建立一种机制，通过这种机制，高中生可以接触到前沿的学术研究，从而促进科学研究的职业道路。获得NSF奖后，Biscoe教授正在研究钯催化的交叉偶联反应中立体烷基单位的转移。本研究的重点是在交叉偶联反应中使用富集对映体的烷基碳丁烷。这些研究探讨了影响碳丁烷主链烷基单元立体化学转移的因素。由于烷基转移可以在三维几何形状的保留或反转中发生，因此采用各种机械探针来阐明影响烷基转移途径的潜在化学因素。由于烷基转移到钯是交叉偶联反应催化循环的一个基本步骤，这些研究促进了新的立体特异性交叉偶联反应的发展，这些反应可用于对映选择性或非对映选择性地生成非外消旋分子。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Biscoe, whose laboratory develops new synthetic strategies for use in organic and medicinal chemistry. Two molecules that have the same composition and structure but are mirror images of each other can elicit drastically different biological responses. Consequently, synthetic methods that enable precise control of three-dimensional molecular structure are essential. Metal-catalyzed cross-coupling reactions are routinely employed by medicinal chemists in efforts to produce biologically active compounds. However, these reactions are most reliable for the preparation of flat molecular units, and not for the preparation of three-dimensionally branched molecular structures. Professor Biscoe’s research investigates new strategies towards the preparation of individual mirror images of a branched molecule. From these studies, new chemical reactions are developed that expedite the synthesis of chiral molecules and contribute to the improved safety and efficacy of pharmaceutical and other biologically-relevant compounds emerging from the discovery process. Dr. Biscoe is active in projects that are designed to increase the diversity of students participating in the STEM fields. As part of these outreach activities, Dr. Biscoe is initiating a joint research program between CCNY and the High School for Math, Science, and Engineering (HSMSE) of City College. The goal of this program is to create a mechanism through which high school students can gain exposure to cutting-edge academic research, thereby facilitating a career path in scientific research. With this NSF award, Professor Biscoe is investigating the transfer of stereodefined alkyl units in palladium-catalyzed cross-coupling reactions. This research focuses on the use of enantioenriched alkylcarbastannatranes in cross-coupling reactions. The factors that influence stereochemical transfer from the alkyl unit of the carbastannatrane backbone are explored in these studies. As alkyl transfer can occur with retention or inversion of three-dimensional geometry, a variety of mechanistic probes are employed to elucidate the underlying chemical factors most influential in determining the pathway of alkyl transfer. Because alkyl transfer to palladium is a fundamental step in the catalytic cycle of cross-coupling reactions, these studies facilitate the development of new stereospecific cross-coupling reactions, which can be used to generate non-racemic molecules enantio- or diastereoselectively.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.