With this award, the Chemical Synthesis Program of the Chemistry Division is funding Professor Jeffrey Johnson of the Department of Chemistry at the University of North Carolina at Chapel Hill to develop new catalytic, enantioselective methods for the construction of heterocycles using readily accessible strained building blocks. Prior NSF-funded research has revealed a unique mechanism for tetrahydrofuran-forming annulation reactions between donor-acceptor cyclopropanes and aldehydes. From this point, other useful heterocycle constructions, including asymmetric variants, have been achieved. The mechanistic understanding gained to date is expected to drive the discovery of new reactions that allow simple access to structures not easily reached using existing methods. Examining new chemistry of donor-acceptor cyclopropanes and exploring the reactivity of heretofore unexplored donor-acceptor strained systems is expected to provide a diverse set of reaction products. A complete exploration of the useful yet underutilized "carbon as a nucleofuge" paradigm will lead to useful reaction patterns. Experimentation in these areas will also provide fertile ground for fundamental studies of reaction mechanism in transformations that involve ground state-destabilized building blocks.
The development of a general platform for heterocycle construction using strained ring activation is of fundamental importance to organic and medicinal chemists. The exploration of myriad activation modes for the donor-acceptor substrates is likely to enhance adoption of the methodology in academic and industrial laboratories. Graduate student coworkers will become adept at a broad range of synthetic and analytical techniques that can be applied to a variety of problems. Through the continued inclusion of student researchers via the AVS Project SEED program, ethnic minorities that are historically underrepresented in the sciences will have access to cutting edge, yet tractable science.
