Tandem Alkene and Diene Isomerization/functionalization Strategy for the Synthesis of Saturated Heterocycles

Auburn University, Auburn AL

Investigators

Abstract

With the support of the Chemical Synthesis Program of the Division of Chemistry, Professor Rashad Karimov of the Department of Chemistry and Biochemistry, Auburn University is studying new catalytic methods to build complex, non-aromatic heterocycles — structural motifs commonly found in medicines and natural products. The goal of this research is to improve how these molecules are made, with a focus on introducing chemical groups at a later stage in the synthesis process. This approach can speed drug discovery by allowing scientists to explore how small chemical changes affect biological activity more efficiently. It can also help researchers more efficiently build bioactive molecules found in nature. As part of the broader impacts, the project will involve mentoring undergraduate and graduate students and engage the public through community-based science outreach programs. These efforts aim to strengthen the scientific workforce and increase public understanding of the role of chemistry in improving human health. This research will develop enantioselective tandem functionalization strategies for the late-stage functionalization of partially saturated heterocycles containing nitrogen, oxygen, or sulfur atoms. Two complementary approaches will be pursued: (1) asymmetric alkene isomerization followed by functionalization to access stereochemically rich five- to eight-membered heterocycles, and (2) asymmetric diene isomerization strategies followed by functionalization enabling regio- and stereoselective cycloaddition and diene functionalization reactions. These catalytic methods leverage the reactivity of in situ-generated polarized alkenes and dienes to install stereocenters adjacent to heteroatoms, addressing long-standing synthetic challenges. The anticipated outcome is a suite of broadly applicable reactions that expand the synthetic toolkit for medicinal chemistry and natural product synthesis, with a primary emphasis on nitrogen heterocycles. 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.