Catalytic Asymmetric Routes to Structurally Diverse P-Stereogenic Phosphines

Dartmouth College, Hanover NH

Investigators

Abstract

With this award, the Chemical Catalysis Program of the NSF Division of Chemistry is supporting the research of Professor David S. Glueck at Dartmouth College for designing new ways to make chiral phosphines. These molecules are important for asymmetric catalysis, which is employed in the pharmaceutical industry to make molecules with a highly specific shape used in pharmaceuticals. Current ways to prepare chiral phosphines are inefficient and limited to a small number of starting materials. These roadblocks to making chiral phosphines is a limitation to the development of critically important catalysts. Professor Glueck and his research group are developing catalysts that can efficiently make chiral phosphines from a large pool of starting materials by controlling the formation of phosphorous-carbon bonds. This project is also providing training for graduate and undergraduate researchers, as well as broadening the participation of underrepresented groups, especially Native Americans, in chemistry, education, and research. Asymmetric transition-metal catalysis is used for the synthesis of single-enantiomer drugs. Chiral non-racemic phosphines are key components of these catalysts but have limited structural diversity due to challenges with asymmetric phosphine synthesis. Since the activity and selectivity of the asymmetric transition metal catalysts are intimately linked to the structure of the chiral phosphines, better ways to make these molecules will support new transition metal catalyzed asymmetric processes. Professor Glueck and his research group are developing several new ways to prepare chiral non-racemic phosphines including: transition metal catalyzed phosphine and diphosphine alkylation, and phosphirane ring-opening. Studies to understand the dynamic and cooperative stereochemical effects in these transformations are also being explored. More sustainable earth-abundant first-row transition metal catalysts are being targeted for these transformations to facilitate ligand substitution and turnover. These research activities serve as a training ground for a diverse group of graduate and undergraduate students. 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.