This project addresses the identification of new catalysts and catalytic methods for preparing valuable enantioenriched acyclic and heterocyclic molecules through the activation of carbon-carbon pi bonds for attack by external heteroatom nucleophiles. The scope of the asymmetric synthesis of enantioenriched branched allylic amines, esters and ethers catalyzed by palladacyclic cobalt oxazoline (COP) complexes will be defined. The use of this chemistry for constructing cyclic molecules such as lactones and cyclic ethers and nitrogen heterocycles will be defined. Mechanistic investigations of the COP-catalyzed synthesis of enantioenriched allylic esters and phenols will be undertaken in order to facilitate discovery of improved catalysts and allow the rational design of new reactions that proceed by similar pathways. An important objective of the proposed investigations is to identify simpler, less expensive catalysts. The use of asymmetric Pd(II) and related catalysts for stereocontrolled construction of heterocycles by cascade ring-forming processes will also be explored.
To increase selectivity and safety, new pharmaceuticals introduced into clinical practice are increasingly complex chiral molecules marketed as single enantiomers. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Larry E. Overman, of the Department of Chemistry at the University of California at Irvine. Professor Overman and his students are studying the use of compounds containing palladium to effect the selective synthesis of chiral organic molecules. The proposed program of research is expected to provide the pharmaceutical industry with new tools for the synthesis and discovery of single enantiomer drugs.
