New advances in (4+3)-Cycloadditions

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Dr. Michael Harmata of the University of Missouri-Columbia is developing new methods for the construction of molecules containing rings of atoms. Molecular rings are found in many compounds that possess significant biological activity and are potentially applicable to human health. Examples include colchicine, used in the treatment of gout, and the experimental resiniferatoxin, a lead compound in the treatment of pain. Molecular rings are also of interest in the development of new materials. In addition to synthesizing these compounds, Dr. Harmata is investigating the how the reactions progress. Certain molecules have a 3-dimentional structure that makes them non-superimposable on their mirror image, just as right and left hands are not superimposable on each other. Dr. Harmata is developing methods to control which mirror image product is formed. Because the different mirror image forms of a molecule can have very different biological activity, the methods Dr. Harmata developed have broad, general significance. Dr. Harmata is also engaged in activities directed towards younger chemists and the general public. He organizes a symposium called Organic Chemistry Day to bring chemists from Missouri and neighboring states together to talk about organic chemistry frontier. Dr. Harmata also speaks at a program at the University of Missouri called Saturday Morning Science. These outreach activities enable him not only to teach organic chemistry, but to explain how research is done and how it serves the general public, sometimes to children as young as six or seven years old. Last but not the least, Dr. Harmata sponsors a summer program for underrepresented high school students to work in his lab. Dr. Harmata is studying two unique (4+3)-cycloaddition reactions. The first synthetic scheme is an asymmetric, catalytic process. Expanding the scope of this process beyond cyclopentenyl oxyallylic cations that are currently being used and understanding the origins of the high enantiocontrol observed are being investigated both experimentally and computationally. The second area makes use of developing oxidopyridinium ions as dienophiles in (4+3)-cycloadditions. This research is being pursued at the most fundamental levels, developing tools for simple stereoselection as well as the control of diastereoselectivity and enantioselectivity. For all of the reactions mentioned, the investigations include both intermolecular and intramolecular prospects. Finally, unique aspects of these reactions are being studied. These include chemical modification of the products to produce reactive species such as strained alkenes and radicals that allow the synthesis of molecules of greater structural complexity. 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.