By Anna Davis

UVA ChemSciComm

These summaries describe a research project for five different levels of understanding, going from primary school to expert.

Primary School:

Everything in the world around you is made up of atoms: tiny bits of matter with different characteristics that link together to form everything you can possibly think of, both on and off the earth. A group of atoms linked together is called a molecule, and the shape of a molecule is one of the biggest factors in determining what it does. As a chemist, it’s my job to figure out ways to make molecules in very specific shapes, so they can be used in medicines or help make other molecules like fuels. Two of the most common and important shapes for atoms in a molecule to form are pentagons and hexagons. I work on different ways to make each of these molecular shapes more efficiently. By mixing specific molecules together at a certain temperature, or in the presence of other molecules that help them bond together, I am finding new ways to form the right shapes in my molecules so that they’re useful to other scientists and society as a whole.

High School:

If you have seen the molecular structure of any drug or natural compound, chances are you’ve noticed how prevalent five- and six-membered rings are in their complex frameworks. As a chemist, I work on developing new chemical reactions to help synthesize these structures to develop useful molecules like medicines and fuels. A cycloaddition is a type of chemical reaction that happens when the electrons of linear molecules move in a cycle to form a ring. These reactions are described by the number of atoms they incorporate from separate molecules to form a ring: for instance, [4+2] cycloadditions bring together a molecule with four carbons and a molecule with two carbons to form a hexagonal six-membered) structure. Normally these reactions take a long time and lots of heat to proceed because of their high activation energy (the barrier which separates the six-membered product from the four carbon and two carbon molecules), so I use an acid catalyst, which lowers the energy so the reaction proceeds more quickly. I also work on a [2+2+1] cycloaddition to form a five-membered ring, bringing together three molecules to form a pentagonal structure with four carbon atoms and one nitrogen atom in it. To help catalyze this reaction, I use various different transition metal-containing compounds.

College:

As you probably learned in organic lecture, the Diels-Alder reaction is one of the most important and versatile reactions known to organic chemists. We have taken weakly dienophilic vinylpyridines and other dienophiles functionalized with aromatic, nitrogen-containing rings, and made them more reactive toward the Diels-Alder by adding in a Lewis acid catalyst. This catalyst works by making the dienophilic alkene more electron deficient, so it more readily reacts with a variety of more electron-rich dienes. We are also working on a different ring-forming reaction with similar cyclic electron movement called a Pauson-Khand reaction. This cycloaddition forms a five-membered ring (instead of the Diels-Alder’s six-membered ring) by joining an alkene, an alkyne, and carbon monoxide. Instead of carbon monoxide, however, we are using a nitrogen-containing reagent that reacts similarly in hopes that we can form a five-membered ring with a nitrogen atom in it, which can be helpful to chemists synthesizing molecules with such a ring in their structure.

Graduate Student in the Discipline:

Inspired by Lewis acid activation of a,b-unsaturated carbonyls as dienophiles in the Diels-Alder reaction, we have expanded into the analogous reaction of a,b-unsaturated imines, namely vinylpyridines. We are able to utilize vinylpyridines and other vinyl N-heterocycles as dienophiles with a variety of sterically and electronically varying dienes, establishing a scope with applications to natural product and pyridine ligand synthesis. We are also developing a variation of a lesser-known named reaction called the Pauson-Khand cycloaddition, in which an alkene, an alkyne, and carbon monoxide form a five-membered cyclopentenone ring. Using a nitrogen-containing precursor that exhibits similar reactivity at the nitrogen center to the carbon of carbon monoxide, we hope to be able to regio- and stereoselectively form functionalized dihydropyrrole rings.

Expert in the Field:

Using main group Lewis acids and transition metal catalysts, my work focuses on the stereoselective formation of carbon-carbon bonds through named cycloaddition reactions.  Specifically, we have developed a Diels-Alder reaction of vinylazaarenes such as 2- and 4-vinylpyridines in which the Lewis basic nitrogen lone pair complexes to BF3-OEt2, thus lowering the LUMO of the dienophilic alkene and activating it towards [4+2] cycloaddition with a wide variety of unactivated dienes with a moderate to high degree of regio- and diastereoselectivity. We have also begun work on an aza-Pauson-Khand reaction in which a transition metal catalyst facilitates the [2+2+1] cycloaddition of an alkene, an alkyne, and a nitrene equivalent to form a functionalized dihydropyrrole.  We hope to expand both these methodologies to asymmetric syntheses soon with the use of chiral ligands.