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，该过程可以更有效地制备重要类别的所谓“杂环”分子。目标杂环化合物具有作为治疗剂、农用化学品和先进材料的潜在应用，因此研究成果可能具有多种社会效益。通过设计具有非常规特性的新型钯配体，可以实现潜在的进步。通过假设驱动和数据驱动的配体设计策略，Paradine 实验室期望发现选择性且广泛有用的反应，从而对感兴趣的分子的特性进行精细调整。在开展研究活动的同时，帕拉丁博士将扩大对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一门正式的科学传播课程。这些活动旨在支持化学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，并使各种背景的学生具备在广泛的环境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合成有机化学多种实用方法的引入。事实上，Pd 催化方法已经普遍用于构建富含 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，富含电子的大体积配体（例如膦和 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钯配体空间的其他领域在很大程度上未被探索，为反应发现留下了相当多的机会，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问题，该资助项目涉及对源自脲和膦的非常规配体平台的研究，以促进钯催化的选择性烯烃双官能化反应，重点是导致非平面杂环支架的杂环化过程。该研究分为四个目标：(1) 开发涉及双亲物（例如 2-溴苯胺）和 1,3-二烯的尿素配体杂环化反应； (2) 探索新型 pi 偶联伙伴与尿素 Pd 催化的反应性； (3)阐明脲配体的基本性质及其催化作用； (4)在烯烃官能化反应中实现配体控制的位点选择性。追求这些目标将包括为配体设计建立数据驱动的预测模型，这些模型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好处。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。