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.

在化学催化计划的支持下，俄亥俄州立大学的David Nagib教授将开发新的催化策略，以合成含有环丙烷，三原子碳碳的有机分子。这些紧张的环分子是在药物活性化合物中发现的最常见的基序之一。但是，很少有制造它们的方法 - 这些方法通常需要使用难以扩展的不稳定试剂。该项目旨在通过采用安全，廉价的起始材料的新催化方法生成环丙烷，并提供综合进入以前无法访问的替代模式。这些研究还将着重于开发有效，可扩展和环境良性的技术，这些技术通常可以应用于可以使社会受益的不同类别的分子的合成。该计划还为一支多样化，充满活力的研究生和本科生团队提供了培训，他们对外展，招聘和启发未来的科学家都充满热情。启发公众的机制包括及时有关与社会相关化学的时事的社交媒体教程。纳吉布教授及其研究团队将研究新的催化策略，以综合环丙烷，这是生物活性小分子的宝贵图案。环丙烷最常通过烯烃和高反应性卡宾中间体的A（2+1）反应合成。当前生成碳纤维的方法需要使用通常不稳定和专业的前体的试剂，并为其进一步应用带来了重大障碍。该提案旨在制定新的催化策略，以使用可持续试剂从更简单，安全和丰富的先驱那里获取碳纤维。这些努力包括亲电金属碳烯的极性逆转，单电子转移事件向自由基中间体，以及开发更适合应用于生物催化和高通量实验等应用的稳健条件。有时可以更轻松地扩大这些过程，以使对医学，材料和农业化学具有广泛影响的新分子的访问更好，更便宜。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的审查标准通过评估来进行评估的。