Cyclopropanations via Non-Stabilized Carbenes

在化学系化学催化项目的支持下，俄亥俄州立大学的David Nagib教授将开发新的催化策略来合成含有环丙烷和三原子碳环的有机分子。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。然而，制造它们的方法很少--这些方法通常需要使用不稳定的试剂，这些试剂很难规模化。该项目寻求用新的催化方法产生环丙烷，这种方法使用安全、廉价的起始材料，并提供合成进入以前无法获得的替代模式。这些研究还将侧重于开发高效、可扩展和环境友好的技术，这些技术通常可以应用于合成不同类别的分子，从而造福社会。该项目还为研究生和本科生组成的多样化和充满活力的团队提供培训，他们也对拓展、招聘和激励未来的科学家充满热情。在激励公众的机制中，有及时的社交媒体教程，介绍与社会相关的化学事件。在这个奖项下，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。环丙烷通常是通过烯烃和高活性卡宾中间体的(2+1)反应合成的。目前产生卡宾的方法需要使用通常不稳定和专门的前体试剂，这给它们的进一步应用带来了巨大的障碍。该建议旨在开发新的催化策略，利用可持续试剂从更简单、更安全和更丰富的前体中获取卡宾。这些努力包括亲电金属卡宾的极性反转，向自由基中间体的单电子转移事件，以及开发适合于生物催化和高通量实验等应用的更稳健的条件。这些过程最终可以更容易地放大，以允许更好、更便宜地获得对医药、材料和农业化学具有广泛影响的新分子。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.