Cyclopropanations via Non-Stabilized Carbenes

通过不稳定的卡宾进行环丙烷化

• 批准号: 2400304
• 负责人: David Nagib
• 金额: $ 59.5万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2400304&HistoricalAwards=false
• 关键词: Cyclopropanations; via; Non; Stabilized; Carbenes

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor David Nagib of Ohio State University will develop new catalytic strategies to synthesize organic molecules containing cyclopropanes, three-atom carbocycles. These strained ring molecules are among the most common motifs found in medicinally active compounds. Yet, there are few methods of making them – and these methods typically require the use of unstable reagents that are difficult to scale. This project seeks to generate cyclopropanes with new catalytic approaches that employ safe, cheap starting materials and provide synthetic entry into substitution patterns that were previously inaccessible. These studies will also focus on developing efficient, scalable, and environmentally benign technologies that can be generally applied to the synthesis of different classes of molecules that can benefit society. The program also provides training for a diverse and dynamic team of graduate and undergraduate students, who are also passionate about outreach, recruitment, and inspiring future scientists. Among the mechanisms for inspiring the public are timely social media tutorials on current events with relevant chemistry to society.Under this award, Professor Nagib and his research team will investigate new catalytic strategies to synthesize cyclopropanes, valuable motifs in bioactive small molecules. Cyclopropanes are most commonly synthesized via a (2+1) reaction of an alkene and a highly reactive carbene intermediate. Current approaches to generating carbenes require the use of reagents that are often unstable and specialized precursors, presenting significant barriers to their further application. This proposal aims to develop new catalytic strategies to access carbenes from more simple, safe, and abundant precursors using sustainable reagents. These efforts include the polarity reversal of electrophilic metallocarbenes, single-electron transfer events to radical intermediates, and developing more robust conditions amenable to applications such as biocatalysis and high-throughput experimentation. These processes can eventually be scaled-up more easily to allow better and cheaper access to new molecules with broad implications for medicinal, materials and agro-chemistry.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.

在化学系化学催化计划的支持下，俄亥俄州州立大学的大卫Nagib教授将开发新的催化策略来合成含有环丙烷，三原子碳环的有机分子。这些应变环分子是在医学活性化合物中发现的最常见的基序之一。然而，制造它们的方法很少-这些方法通常需要使用难以规模化的不稳定试剂。该项目旨在用新的催化方法产生环丙烷，这些方法采用安全，廉价的起始材料，并提供合成进入以前无法进入的取代模式。这些研究还将侧重于开发高效、可扩展和环境友好的技术，这些技术通常可用于合成不同类别的分子，从而造福社会。该计划还为多样化和充满活力的研究生和本科生团队提供培训，他们也热衷于推广，招聘和激励未来的科学家。在激励公众的机制中，包括及时的社交媒体教程，介绍与社会相关的化学时事。根据该奖项，Nagib教授和他的研究团队将研究合成环丙烷的新催化策略，环丙烷是生物活性小分子中有价值的基序。环丙烷最常通过烯烃和高反应性卡宾中间体的（2+1）反应合成。目前生成卡宾的方法需要使用通常不稳定和专用前体的试剂，这对它们的进一步应用构成了重大障碍。该提案旨在开发新的催化策略，以使用可持续的试剂从更简单，安全和丰富的前体获得卡宾。这些努力包括亲电性双卡宾的极性反转，自由基中间体的单电子转移事件，以及开发更稳健的条件，适用于生物催化和高通量实验等应用。这些过程最终可以更容易地扩大规模，从而更好、更便宜地获得对医药、材料和农业化学具有广泛意义的新分子。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审查标准进行评估，被认为值得支持。