New Hypervalent Iodine Agents for N-N Bond Coupling

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry Professor Song Lin of Cornell University is developing new chemical reactions that form nitrogen–nitrogen (N–N) bonds. N–N bonds are frequently present in useful organic compounds such as bioactive natural products, medicines, agrochemicals, and polymer materials. However, traditional approaches to construct N–N bonds are significantly limited by the types of products that they can provide. The Lin lab aims to develop a new reagent that can selectively couple two molecules containing amines, which are readily available species from feedstock chemicals and naturally occurring compounds. The long-term objective of this research program is to facilitate the development of new medicines, agrochemicals, and light-responsive materials. The project lies at the interface of organic synthesis, medicinal chemistry, and physical organic chemistry. Therefore, it is also well suited for the education of trainees including graduate and undergraduate students. In addition to contributing to the advancement of scientific knowledge and improving fine chemical preparation, the project will also exert broader impacts on the training of students through collaboration with other laboratories with complementary expertise. Professor Song Lin is studying the development of reaction methodologies using novel hypervalent iodine agents for the selective coupling of amines. N–N bonds are prevalent in bioactive natural products, medicinal agents, agrochemicals, and functional materials. An efficient and modular approach to synthesizing N–N containing molecules is the direct coupling of two N-containing fragments. Currently available protocols for N–N coupling predominantly focus on amides, imines, or arylamines as substrates. The direct coupling of unactivated aliphatic amines would drastically improve the synthetic scope of this bond disconnection strategy but such transformations remain elusive. To this end, the Lin lab will develop hypervalent iodine reagents with labile ligands to promote N–N coupling reactions to access important target products, including natural products, medicinal agents, and photoresponsive materials. Finally, the Lin lab will develop experimental modules on the basis of proposed N–N coupling reactions to synthesize photoresponsive compounds and use them in outreach events with high school students. 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.