Grant: Discovery Grants Program - Individual

The proposed research program is designed to study methodologies that should improve the Henry reaction. This chemical reaction generates key synthetic intermediates that can be used in the pharmaceutical industry. For example, 1,2-aminoalcohol functionality can be produced after reduction of the Henry reaction product. This functionality is found in chemicals that can affect neurotransmission and is found in Tamiflu, the only drug that is believed to stop avian flu. The Henry reaction has inherent thermodynamic problems. To solve these problems, the nitroalkane used in the reaction is used in large excess, and thus complex large nitroalkane reagents cannot be used in the reaction and intramolecular reactions a very difficult to perform. To solve this problem, we propose to modify the reaction conditions use either silyl nitronates or boron nitronates. These modifications should allow for less equivalents of the nitroalkane within the reaction conditions and thus allow researchers to use more complex starting materials. More importantly, intramolecular reactions should now become accessible and create new synthetic routes for Tamiflu, which presently has a severe supply problem. During this research program, the stereochemical outcome of these new reactions will also be probed. This work will also provide university students the opportunity to gain valuable experience in synthetic organic chemistry and enhance their problem solving skills