Cyclopropanations via Non-Stabilized Carbenes

Ohio State University, The, Columbus OH

Investigators

Abstract

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.