Conjugate addition coupled to cationic cyclization: new methods for small molecule synthesis

共轭加成与阳离子环化：小分子合成的新方法

• 批准号: 1900050
• 负责人: Alison Frontier
• 金额: $ 49万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900050&HistoricalAwards=false
• 关键词: Conjugate; addition; coupled; cationic; cyclization

With this Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Alison Frontier of the University of Rochester, whose research program is focused on building small molecules with different three-dimensional architectures. The spatial array of carbon, nitrogen and oxygen atoms of molecules is critical to the behavior of the molecules, specifically, their reactivity in different environments, and their ability to bind to other molecules. However, many natural and man-made molecules with potential uses as materials, catalysts, or pharmaceutical agents, are difficult to prepare using existing chemical protocols. The research conducted by Professor Frontier and her students expands the range of three-dimensional molecules that can be assembled using chemical methods, and at the same time, develops chemical reactions that have not been previously described. Through methods that form several new bonds in a single, controlled process, the group develops chemical strategies useful in a broad set of applications. Professor Frontier also continues to develop and maintain the "Not Voodoo" website, an educational resource. The site is designed to help students demystify laboratory protocols and procedures. It serves hundreds of organic experimental chemists each day, from students just beginning independent research, to advanced students looking for more efficient synthetic methods. Synthetic chemists are constantly searching for versatile new methods for building densely functionalized molecules containing bridged, spirocyclic and fused ring systems, ideally with heteroatoms embedded in the scaffold of the three-dimensional molecules. The new methods Professor Frontier and her students are studying simplify the synthesis of targets with unusual, densely functionalized ring systems, including cycloheptane systems and nitrogen-rich heterocycles. Novel pericyclic reactions are being developed in the context of reaction cascades that build complex ring systems from simple precursors, with the formation of up to three carbon-carbon or carbon-nitrogen bonds in one synthetic operation. Given the stereochemical control imparted by these pericyclic processes, the work represents efforts to develop efficient, stereoselective reaction sequences while garnering a new understanding of the factors critical to successful multi-step processes with pericyclic components. Students engaged in this work learn to devise synthetic strategies, analyze complex reaction outcomes ,and characterize small three-dimensional molecules. Professor Frontier's long-standing website project (Not Voodoo: Demystifying Synthetic Organic Chemistry) provides a resource for students learning laboratory techniques for the first time, and supporting more advanced students seeking to explore unfamiliar territory in their experimental work.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.

有了这个奖项，NSF化学部的化学合成计划支持罗切斯特大学的Alison Frontier教授的研究，他的研究计划专注于构建具有不同三维结构的小分子。 分子的碳、氮和氧原子的空间排列对于分子的行为至关重要，特别是它们在不同环境中的反应性以及它们与其他分子结合的能力。然而，许多具有潜在用途的天然和人造分子，如材料、催化剂或药剂，难以使用现有的化学方案制备。 Frontier教授和她的学生进行的研究扩大了可以使用化学方法组装的三维分子的范围，同时开发了以前没有描述过的化学反应。 通过在一个单一的控制过程中形成几个新键的方法，该小组开发了在广泛应用中有用的化学策略。Frontier教授还继续开发和维护“Not Voodoo”网站（一种教育资源）。 该网站旨在帮助学生揭开实验室协议和程序的神秘面纱。它每天为数百名有机实验化学家提供服务，从刚刚开始独立研究的学生到寻找更有效合成方法的高级学生。合成化学家一直在寻找多功能的新方法，用于构建含有桥连、螺环和稠环系统的密集官能化分子，理想情况下，杂原子嵌入三维分子的支架中。Frontier教授和她的学生正在研究的新方法简化了具有不寻常的、密集官能化的环系统的目标的合成，包括环庚烷系统和富氮杂环。 新型周环反应是在反应级联的背景下开发的，该反应级联从简单的前体构建复杂的环系统，在一个合成操作中形成多达三个碳-碳或碳-氮键。 鉴于这些周环过程赋予的立体化学控制，这项工作代表了努力开发有效的，立体选择性的反应序列，同时获得了一个新的理解的因素，成功的多步骤工艺与周环组件。 从事这项工作的学生学习设计合成策略，分析复杂的反应结果，并表征小的三维分子。Frontier教授的长期网站项目（Not Voodoo：Demystifying Synthetic Organic Chemistry）为首次学习实验室技术的学生提供了资源，并支持更先进的学生在他们的实验工作中探索不熟悉的领域。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

“The Chemistry of Poisons”: An Interdisciplinary Approach to Integrating Chemical, Toxicological, and Medicinal Principles

– 毒物化学 –：整合化学、毒理学和医学原理的跨学科方法

• DOI: 10.1021/acs.jchemed.0c00231
• 发表时间: 2020
• 期刊: Journal of Chemical Education
• 影响因子: 3
• 作者: Austin, Daniel;Frontier, Alison J.
• 通讯作者: Frontier, Alison J.

One-Pot Double-Annulation Strategy for the Synthesis of Unusual Fused Bis-Heterocycles

• DOI: 10.1021/acs.orglett.0c01351
• 发表时间: 2020-06-05
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Abdul-Rashed, Shukree;Alachouzos, Georgios;Frontier, Alison J.
• 通讯作者: Frontier, Alison J.