CAREER: Establishing Ligand Platforms to Enable Selective, Catalytic Olefin Difunctionalization Reactions for Constructing Diverse Heterocyclic Scaffolds

职业：建立配体平台以实现选择性催化烯烃双官能化反应，以构建多种杂环支架

• 批准号: 2238081
• 负责人: Shauna Paradine
• 金额: $ 77万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2238081&HistoricalAwards=false
• 关键词: CAREER; Establishing; Ligand; Platforms; Enable

With the support of the Chemical Synthesis Program in the Division of Chemistry, Shauna Paradine of the University of Rochester is studying new metal-catalyzed chemical processes that may enable more efficient preparation of important classes of so-called 'heterocyclic' molecules. The kinds of heterocycles being targeted have potential applications as therapeutic agents, agrochemicals, and advanced materials, and as such the outcome of the research could have a variety of societal benefits. The potential advances being offered are made possible with the design of new ligands for palladium that possess unconventional properties. Through both hypothesis-driven and data-driven ligand design strategies, the Paradine laboratory expects to discover selective and broadly useful reactions that will allow for refined tuning of the properties of the molecules of interest. In parallel with research activities, Dr. Paradine will expand mentoring experiences for chemistry graduate students at the University of Rochester and develop a formal course in scientific communication for undergraduate and graduate students. These activities are designed to support the personal and professional development of chemistry students, with a special focus on addressing the needs of students from marginalized groups, and to equip students of all backgrounds with the capacity to be effective scientific communicators in a broad range of contexts and media.The ability of palladium to form broadly reactive organometallic species has led to the introduction of a diverse array of practical methodologies for synthetic organic chemistry. Indeed, Pd-catalyzed methods have become ubiquitous for the construction of molecular scaffolds rich in sp2-hybridized carbon atoms. Ligand development has been a key driver of this innovation, with electron-rich and bulky ligands such as phosphines and N-heterocyclic carbenes being predominantly used in efforts to uncover new Pd-catalyzed reactivity. However, the success of these ligand families has led to other areas of ligand space for palladium being left largely unexplored, leaving considerable opportunities for reaction discovery, particularly in regard to methods for the construction of sp3-hybridized carbon-rich domains. To address this imbalance, the funded project involves study of unconventional ligand platforms derived from ureas and phosphines to facilitate Pd-catalyzed selective olefin difunctionalization reactions, with an emphasis on heteroannulation processes leading to non-planar heterocyclic scaffolds. The investigation is divided across four aims: (1) development of urea ligand-enabled heteroannulation reactions involving ambiphiles (e.g., 2-bromoanilines) and 1,3-dienes; (2) exploration of the reactivity of new pi-coupling partners with urea-enabled Pd catalysis; (3) elucidation of the fundamental properties of urea ligands and their role in catalysis; and, (4) realization of ligand-controlled site-selectivity in olefin functionalization reactions. Pursuit of these aims will include the foundation of data-driven, predictive models for ligand design that are anticipated to facilitate general strategies for ligand development in the field of transition metal catalysis with associated benefits for future reaction discovery.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.

在化学系化学合成项目的支持下，罗切斯特大学的Shauna Paradine正在研究新的金属催化化学过程，这可能使重要类别的所谓“杂环”分子的制备更加有效。被靶向的杂环种类具有作为治疗剂、农用化学品和先进材料的潜在应用，因此研究结果可能具有各种社会效益。所提供的潜在的进步是可能的钯，具有非常规性能的新配体的设计。通过假设驱动和数据驱动的配体设计策略，Paradine实验室希望发现选择性和广泛有用的反应，这些反应将允许对感兴趣分子的性质进行精细调整。在研究活动的同时，Paradine博士将扩大罗切斯特大学化学研究生的指导经验，并为本科生和研究生开发科学交流的正式课程。这些活动旨在支持化学专业学生的个人和专业发展，特别注重满足边缘群体学生的需求，并使所有背景的学生具备在广泛的背景和媒体中成为有效的科学传播者的能力。钯形成广泛反应性有机金属物种的能力导致了各种各样的实用合成有机化学方法学。事实上，钯催化的方法已经成为无处不在的构建富含sp2杂化碳原子的分子支架。配体开发一直是这一创新的关键驱动力，富电子和庞大的配体，如膦和N-杂环卡宾，主要用于发现新的Pd催化反应性。然而，这些配体家族的成功导致了钯的配体空间的其他领域在很大程度上未被探索，留下了相当多的反应发现的机会，特别是在构建sp3杂化富碳结构域的方法方面。为了解决这种不平衡，资助的项目涉及来自脲和膦的非常规配体平台的研究，以促进Pd催化的选择性烯烃双官能化反应，重点是杂环化过程导致非平面杂环支架。该研究分为四个目标：（1）开发涉及两亲物（例如，2-溴苯胺）和1，3-二烯;（2）探索新的π-偶联配偶体与脲使能的Pd催化剂的反应性;（3）阐明脲配体的基本性质及其在催化中的作用;以及（4）在烯烃官能化反应中实现配体控制的位点选择性。这些目标的追求将包括数据驱动的配体设计预测模型的基础，预计将促进过渡金属催化领域配体开发的一般策略，并为未来的反应发现带来相关利益。该奖项反映了NSF的法定使命，并被认为值得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来支持。