Stereodivergent Approaches to Pd-Catalyzed Cross-Coupling Reactions

Pd 催化交叉偶联反应的立体发散方法

• 批准号: 2247622
• 负责人: Mark Biscoe
• 金额: $ 19.2万
• 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: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247622&HistoricalAwards=false
• 关键词: Stereodivergent; Approaches; Pd; Catalyzed; Cross

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Mark R. Biscoe of the City College of New York (CCNY) is studying so called 'cross-coupling reactions' that are important carbon-carbon bond forming reactions in synthetic chemistry, with relevance to a broad range of applications, including pharmaceutical, agricultural and materials chemistry. Two molecules that ostensibly have the same composition and structure but which are mirror images of each other, can elicit very different biological responses. Consequently, synthetic methods that enable precise control of three-dimensional molecular structure are essential to the fields of chemical biology and medicinal chemistry. The chemical processes under development in this research embody a versatile strategy wherein a single precursor building block can be used to access either mirror image form of a desired target molecule. Arriving at this level of control will require advances in the fundamental understanding of the molecular-level mechanisms that underpin the cross-coupling reactions of interest. The new methods emerging from the supported studies are anticipated to be broadly enabling for stereoselective synthesis. The broader impacts of the project are extended by a range of educational and outreach activities that Professor Biscoe and his team of coworkers are engaged in that are designed to increase the diversity of students participating in the science and engineering enterprise. As part of these outreach efforts, Professor Biscoe has initiated a joint research program between CCNY and the High School for Math, Science, and Engineering (HSMSE) of City College. The goal of this endeavor is to create a means through which high school students can gain exposure to cutting-edge academic research, thereby potentially fostering their interest in pursuing future careers in science-related fields.Under this award, the Biscoe team will be focused on the study and development of stereodivergent palladium-catalyzed cross-coupling reactions from stereochemically defined gem-dimetallated alkyl nucleophiles. Boron, germanium, and tin constitute the main group metals contained within the enantioenriched gem-dimetallated nucleophiles of interest and new methods to access these versatile synthons will be investigated alongside their deployment in a variety of cross-couplings (e.g., Suzuki-Miyaura and Stille reactions). It is envisioned that the strategic application of stereodefined gem-dimetallated alkyl nucleophiles in iterative stereospecific cross-coupling processes will enable precise control of three-dimensional molecular structure in a reliable and general manner. Because alkyl transfer can occur with retention or inversion of stereochemical configuration, the mechanism of the transmetallation step from the gem-dimetal species will be probed in detail to facilitate the development of synthetic tactics through which both enantiomers of a desired cross-coupling product can be accessed from a single enantioenriched precursor. Due to the fact that nucleophile transfer to palladium is a fundamental step in the catalytic cycle of cross-coupling reactions, it is anticipated that the new knowledge gained from this exercise will lead to significant advances in technology for the stereoselective formation of carbon-carbon bonds.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.

在化学系化学合成计划的支持下，纽约城市学院(CCNY)教授Mark R.Biscoe正在研究所谓的交叉偶联反应，这是合成化学中重要的碳-碳键形成反应，与广泛的应用有关，包括制药、农业和材料化学。两个分子表面上具有相同的组成和结构，但实际上却是彼此的镜像，它们可能会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对于化学生物学和药物化学领域是必不可少的。这项研究中正在开发的化学过程体现了一种多功能的策略，其中单个前体构建块可以用于访问所需目标分子的任一镜像形式。要达到这种水平的控制，就需要对支撑感兴趣的交叉偶联反应的分子水平机制的基本理解取得进展。从所支持的研究中出现的新方法预计将广泛地使立体选择性合成成为可能。比斯科教授和他的同事团队参与的一系列教育和外联活动扩大了该项目的更广泛影响，这些活动旨在增加参与科学和工程事业的学生的多样性。作为这些外展工作的一部分，比斯科教授发起了CCNY和城市学院数学、科学和工程高中(HSMSE)的联合研究计划。这项工作的目标是创造一种方法，通过这种方法，高中生可以接触到尖端的学术研究，从而潜在地培养他们在未来科学相关领域追求职业生涯的兴趣。在这个奖项下，Biscoe团队将专注于从立体化学定义的宝石双金属烷基亲核试剂出发，研究和开发立体发散的钯催化的交叉偶联反应。硼、锗和锡构成了感兴趣的富含对映体的宝石双金属亲核试剂中的主要族金属，获得这些多功能合成子的新方法将被研究，同时它们将被部署在各种交叉偶联中(例如，Suzuki-Miyaura和Stille反应)。可以预见，立体定义的宝石双金属烷基亲核试剂在迭代立体定向交叉偶联过程中的战略应用将使以可靠和一般的方式精确控制三维分子结构成为可能。由于立体化学构型的保留或倒置可能会发生烷基转移，因此将详细探讨宝石-双金属物种的过渡金属步骤的机理，以促进合成策略的发展，通过这种合成策略，所需交叉偶联产物的两个对映体都可以从单一的富含对映体的前体中获得。由于亲核性转移到钯是交叉偶联反应催化循环中的基本步骤，预计从这项工作中获得的新知识将导致碳-碳键立体选择性形成技术的重大进步。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。