New Stereoselective Fragment Coupling Reactions for Organic Synthesis

Northwestern University, Evanston IL

Investigators

Abstract

With this New award, the Chemical Synthesis Program supports Professor Regan J. Thomson of Northwestern University in an investigation of new reactions that enable the coupling of two or more molecular fragments to generate new molecules with specific molecular shapes. These reactions will be especially powerful within the realm of drug discovery, and ultimately facilitate the rate at which new biologically active entities can be prepared for further evaluation. These studies will expose students to a diversity of research areas including synthesis design, catalysis, methodology development, and the use of mass spectrometric techniques to screen products. The undergraduates and graduate students participating in this project will be involved in mentoring the research projects of Chicago area high school students. The project will study new carbon-carbon bond forming reactions utilizing N-allylhydrazones and N-sulfonylhydrazones. The approach will involve the oxidation of allyl hydrazones to diazoallenes, which then undergo a stereoselective [3,3]-rearrangement with the formation of a new carbon-carbon bond ultimately producing carbocations, which can be trapped with external nucelophiles. In addition, sulfonyl hydrazones will be utilized in new carbon-carbon bond forming reactions. These stereoselective fragment coupling reactions will be employed in the systhesis of biologically active natural products.