Metal-Catalyzed Asymmetric Cyclization Reactions

Pennsylvania State Univ University Park, University Park PA

Investigators

Abstract

The objectives of this work are to design and test new transition metal catalysts for effecting asymmetric carbon-carbon bond forming reactions. Two reactions in particular will be studied in detail, asymmetric rhodium catalyzed ene reactions and silver and copper catalyzed asymmetric 1,3 dipolar cycloadditions of azomethine ylides. In each case, new sets of chiral phosphine ligands will be prepared and then an understanding of the mechanisms of these reactions will be used to "fine tune" metal/ligand catalysts systems for these reactions. The rhodium catalyzed enyne cycloisomerization will be applied to asymmetric syntheses of the natural products Oppositol and alpha-Kainic acid. The silver and copper catalyzed reactions will be applied to core structures found in hexahydrotriquinacene, hydantoin, and polycyclic fused lactam containing natural products. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Xumu Zhang of the Department of Chemistry at Penn State University. Dr. Zhang will explore stereoselective cyclization reactions which are catalyzed by rhodium, silver, and copper reagents. The ability to form carbon-carbon bonds in molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer) is one of the most important problems facing the pharmaceutical industry today. When developed, Dr. Zhang's rhodium catalyzed work could be applied to the synthesis of natural products such as Oppositol and alpha-Kainic acid. The marine natural product Kainic acids are potent neurotransmitters and a worldwide shortage of these compounds has hindered work in the neuroscience community. The silver and copper catalyzed reactions will be applied to core structures found in hexahydrotriquinacene, hydantoin, and polycyclic fused lactam containing natural products which have a broad range of biological activities as antivirals, antifungals, antibacterials, and herbicidals. Students trained during the course of this work will gain skills needed by the pharmaceutical industry which now produces a number of single enantiomer compounds.