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

金属催化反应中立体定向烷基转移的新方法：合成和机理研究

基本信息

批准号：
1955472
负责人：
Mark Biscoe
金额：
$ 47万
依托单位：
CUNY City College
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955472&HistoricalAwards=false
关键词：
New Approaches Stereospecific Alkyl Transfer

项目摘要

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.

通过该奖项，NSF化学部的化学合成计划支持Biscoe教授的研究，Biscoe的研究实验室开发了新的合成策略，用于有机和医学化学中。两个具有相同组成和结构但彼此镜像的分子可以引起截然不同的生物学反应。因此，可以精确控制三维分子结构的合成方法至关重要。金属催化的交叉偶联反应通常由药物学家通常使用，以产生生物活性化合物。但是，这些反应对于制备平坦分子单位最可靠，而不是制备三维分支分子结构。 Biscoe教授的研究调查了制备分支分子各个镜像图像的新策略。从这些研究中，开发出新的化学反应，加快了手性分子的合成，并有助于提高药物和其他与生物学相关的化合物的安全性和有效性。 Biscoe博士活跃于旨在增加参与STEM领域的学生多样性的项目。作为这些外展活动的一部分，Biscoe博士是CCNY与城市学院数学，科学和工程学（HSMSE）之间的联合研究计划。该计划的目的是创建一种机制，高中生可以通过该机制获得尖端的学术研究，从而支持科学研究的职业道路。通过这一NSF奖，Biscoe教授正在研究钯催化的交叉偶联反应中立体置换烷基单元的转移。这项研究的重点是在交叉偶联反应中使用元素烯基烷基钙化烷。在这些研究中，探索了影响卡巴斯坦纳塔雷烷基链烷基单位的立体化学转移的因素。由于烷基转移可以随着三维几何形状的保留或反转而发生，因此采用多种机械问题来阐明在确定烷基转移途径时最大程度地影响的基本化学因子。由于烷基转移到钯是交叉偶联反应催化循环中的基本步骤，因此这些研究支持开发新的立体特定特定的交叉偶联反应，可用于生成非种族隔离分子，以产生非遗传性分子，以鉴定和非真实依据。该奖项通过评估了NSF的智力统治，其概述的依据是众所周知的依据。标准。