Among the most demanding challenges in organic chemistry is the introduction of chirality via catalytic methods. This project examines new concepts towards this goal in four disparate areas. The first involves the rational design of ligands for formation of dinuclear and heterodinuclear metal complexes as catalysts for addition reactions. The second area involves asymmetric trimethylenemethane (TMM) cycloadditions. The fact that the addition of the acceptor occurs on the face of the TMM unit distal to where the metal and its attendant ligands reside makes asymmetric induction highly challenging. With the aid of molecular modeling, new ligand families have been designed for [3+2], [3+4], and [3+6] cycloadditions. The third section examines Pd and Mo catalyzed asymmetric allylic alkylation. Using ligand design, contrasteric nucleophilic addition to the more substituted allyl terminus as well as contrathermodynamic addition to the C-2 position of the allyl unit will be attempted. Novel Ru-Pd sequential reactions for asymmetric synthesis will also be studied. The fourth area is the asymmetric induction in Ru catalyzed reactions for their exploration in alkene-alkyne coupling and allylic alkylations.
With this award, the Organic and Macromolecular Chemistry Program supports the research program of Professor Barry M. Trost of the Department of Chemistry at Stanford University. Professor Trost's program revolves around the theme of enhancing synthetic efficiency by inventing new catalytic processes that exercise enhanced chemo-, regio-, diastereo-, and enantio-selectivity. Particular attention focuses on processes that enhance atom economy, a key aspect of "green chemistry". Success has impacts on areas ranging from materials science to biology, especially with respect to the pharmaceutical and agrichemical industries.
Solving societal problems ranging from materials science to biology and medicine resolve down to understanding how molecular structure begets function. One of the most difficult aspects of molecular structure that is particularly fundamental and critical, especially in any biological problems, is the precise three dimensional structure wherein molecules exist in two different mirror isomer forms, comparable to the relationship of one’s right and left hands. This program features the development of the fundamental tools, ie the chemical reactions, that address this most difficult structural challenge synthetically. This program has invented new catalytic chemical processes that enable over twenty synthetic transformations which create uniquely such three dimensional structures and that permits the visualization and implementation of new strategies to complex molecules that either previously did not even exist or to structural types identified through natural products but whose availability from nature precluded their evaluation and development. The discoveries involve the invention of novel catalysts based upon organic structures as well as main group and transition metals. The structural types on which we focus deal principally with problems in biology and medicine. As just one illustration, amino acids and nucleosides are basic building blocks of biological systems. Many important drugs derive from such fundamental types of structures. The methods developed herein provide broad access to both of these structural cores adorned with additional structural complexity to target the resultant structures as drug candidates. Thus, we interact with numerous companies with programs in these areas such as pharmaceutical and agrichemical companies. These catalytic systems have already had use within such industries in the initial and beginning development stages of drug research.
