RUI: Development of Bench-stable N-quaternized ketene N,O-acetals as Multifunctional Reagents for Organic Synthesis

RUI：开发实验室稳定的 N-季铵化乙烯酮 N,O-缩醛作为有机合成多功能试剂

• 批准号: 2155127
• 负责人: Max Majireck
• 金额: $ 24.69万
• 依托单位: Hamilton College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2155127&HistoricalAwards=false
• 关键词: RUI; Development; Bench; stable; quaternized

With the support of the Chemical Synthesis program in the Division of Chemistry, Max Majireck of Hamilton College is studying a new class of compounds that is useful for the manufacture of value-added materials such as pharmaceutical agents, agrochemicals, and other substances of use to society. Central to this research is a recent discovery made by the Majireck research group that reactive compounds known as N-quaternized ketene N,O-acetals, typically too delicate to be handled, can be prepared in a manner that stabilizes them. This important finding opens the door for such materials to be employed for the first time in the synthesis of a broad range of valuable compounds. For example, a goal of the funded project is to use the newly available class of N,O-acetals for the preparation of biologically active nitrogen-containing cyclic compounds commonly found as components in active pharmaceuticals. Furthermore, the research team will investigate a variety of processes involving the new reagents to uncover efficient methods for chemical manufacture that are straightforward and devoid of expensive additives, such as precious metal catalysts. The broader impacts of the project will extend to supporting research-based academic courses and summer research experiences for undergraduate students in synthetic organic chemistry at Hamilton College, with an emphasis on recruiting, training, and retaining students from underrepresented groups for careers in science, technology, engineering, and mathematics (STEM).N-Quaternized ketene N,O-acetals have been overlooked as reagents in organic synthesis due to their typical instability and/or specialized means of generation in situ. However, it was recently discovered that certain compounds within this class, and particularly pyridinium ketene N,O-acetals, have long-term bench-stability that allows for their preparation and purification in a straightforward manner. This opens up the possibility of leveraging N-quaternized ketene N,O-acetals as versatile reagents in organic synthesis. For example, such compounds can act as a source of thermally-generated O-alkyl ketenium ions, which can be used in acid catalyst-free Friedel-Crafts acylations, or in various cycloaddition reactions. Beyond the continued explorations of these kinds of processes, Dr. Majireck and his team of undergraduate students will also study the use of 2-halo-N-(1-alkoxyvinyl)pyridinium salts as electrophiles for the production of 2-aminopyridine derivatives via mild nucleophilic aromatic substitution reactions. The research will provide valuable opportunities for undergraduate students, particularly those from groups traditionally underrepresented in STEM, to partake in immersive research experiences which are anticipated to contribute toward a strengthening and diversification of the U.S. scientific workforce.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，汉密尔顿学院的Max Majireck正在研究一类新的化合物，这些化合物可用于制造增值材料，如药剂，农用化学品和其他社会物质。这项研究的核心是Majireck研究小组最近发现的一种反应性化合物，称为N-季铵化乙烯酮N，O-缩醛，通常过于脆弱而无法处理，可以以稳定它们的方式制备。这一重要发现为此类材料首次用于合成各种有价值的化合物打开了大门。例如，该资助项目的目标是使用新获得的N，O-缩醛类化合物来制备通常作为活性药物成分的生物活性含氮环状化合物。此外，研究小组还将研究涉及新试剂的各种工艺，以发现直接且不含贵金属催化剂等昂贵添加剂的有效化学制造方法。该项目的更广泛影响将扩展到支持汉密尔顿学院合成有机化学本科生的研究型学术课程和夏季研究经验，重点是招募，培训和留住来自代表性不足群体的学生，从事科学，技术，工程和数学（STEM）。O-缩醛由于其典型的不稳定性和/或特殊的原位生成方式，在有机合成中被忽视。然而，最近发现这类化合物中的某些化合物，特别是吡啶鎓烯酮N，0-缩醛，具有长期的工作台稳定性，这允许它们以直接的方式制备和纯化。这开辟了利用N-季铵化烯酮N，0-缩醛作为有机合成中的通用试剂的可能性。例如，这样的化合物可以充当热生成的0-烷基烯酮钥离子的来源，其可以用于无酸催化剂的Friedel-Crafts酰化或用于各种环加成反应。除了继续探索这些过程之外，Majireck博士和他的本科生团队还将研究使用2-卤代-N-（1-烷氧基乙烯基）吡啶盐作为亲电试剂，通过温和的亲核芳香取代反应生产2-氨基吡啶衍生物。这项研究将为本科生提供宝贵的机会，特别是那些传统上在STEM中代表性不足的群体，参与沉浸式研究体验，预计将有助于加强美国科学劳动力的实力和多元化。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响进行评估，被认为值得支持审查的搜索.