This project is focused on developing useful new catalytic ring forming reactions. A detailed plan is put forth to utilize mechanistic insights to design new catalysts for the ring expansion of strained heterocyclic synthons. The information gained from these catalyst design and development studies will be used to build chiral variants of the optimal ligand frameworks. The resulting new chiral catalysts will be used for asymmetric desymmetrizations and kinetic resolutions. Concurrently, new and efficient synthetic routes for assembling these heterocyclic synthons will be developed. This will be accomplished in one pot by adding carbon nucleophiles to uniquely activated carbonyl electrophiles.

With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Jon T. Njardarson of the Department of Chemistry and Chemical Biology at Cornell University. Professor Njardarson's research efforts revolve around the development of new and useful methods for building valuable heterocyclic frameworks. Successful advancement of these new synthetic methods will provide access to a wide range of important heterocyclic products, which will benefit researchers both in academia and the pharmaceutical industry.

Project Report

During the grant period we have developed several unique new organic reactions that offer new approaches to valuable architectural scaffolds that can be utilized for the construction of pharmaceuticals, materials, commodity chemicals as well as academic scientific pursuits. These new reactions fall into two classes: 1) catalytic ring expansion of strained rings and 2) anionic cascades. We have showcased the value of these new reactions with expedient syntheses of several natural products and pharmaceuticals cores. We have gained new insights into the mechanism of our successful copper(II) catalyzed ring expansion reactions that will allow us to design better catalysts and guide us to an asymmetric variant. Our new catalytic ring expansion of four membered rings is mild, broad in scope and its mechanism presented us with a novel route to chiral products. The anionic cascades we reported on recently represent an important new program in our group that is a natural outgrowth of our current efforts and promises to produce a number of useful new reactions as well as valuable new scientific insights. On the educational front we have developed free useful new tools for teaching and research purposes. During the grant period we created the 2008, 2009 and 2010 Top200 drug posters. These popular posters, which can be downloaded for free from our website (http://cbc.arizona.edu/njardarson/group/top-pharmaceuticals-poster) have been downloaded more than 100,000 times since we received support from NSF and are now used for teaching, pharmaceutical research as well as serving as catalysts for new method ideas. We presented this work in J. Chem. Ed. 2010, 87, 1348. I am proud to announce that last summer (2011) we launched a new educational website called CHEMISTRY BY DESIGN (http://chemistrybydesign.oia.arizona.edu/). This website provides advanced undergraduate students, graduate students, post-graduates and professionals with an interactive continuously growing flashcard database of organic syntheses (natural product and pharmaceuticals) that they can use to learn about the wonders of organic chemistry. We have also created free APP versions of the website for iphone, ipad and android users. In the seven months since its launch, more than 120,000 have visited the website and the apps have been downloaded more than 30,000 times. Professors around the US have started to use it for their classes and students and professionals around have joined our educational mission by submitting syntheses of their choice to us that we then upload to the site. Every contributors name is added to an online acknowledgement list. A discussion of this new project has been submitted to the Journal of Chemical Education.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Application #
1120184
Program Officer
Tingyu Li
Project Start
Project End
Budget Start
2010-11-04
Budget End
2012-02-29
Support Year
Fiscal Year
2011
Total Cost
$144,368
Indirect Cost
Name
University of Arizona
Department
Type
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721