With this award, the Chemical Catalysis Program of the Chemistry Division supports the research program of Professor Vladimir Birman. Professor Birman is a faculty member in the Department of Chemistry at Washington University in Saint Louis. Prof. Birman's research interests revolve around chiral organic compounds: compounds whose structures exist as distinct mirror images called enantiomers. The two enantiomers of the same compound often display different biological activities, which becomes vitally important in the case of chiral pharmaceuticals. The wrong enantiomer of a drug may have reduced pharmacological activity or even be toxic. Therefore, there is considerable interest in developing methods for preparing chiral compounds in the form of single enantiomers. Selective catalysis, which is the main focus of research in the Birman group, is an economical and waste-free approach to accomplishing this goal. The present project aims to explore a new family of reactions using Birman's chiral catalysts, which previously were developed in the Birman group and are currently used by many researchers worldwide. These reactions provide access to new classes of chiral compounds that may find applications as drug development and biological studies. Prof. Birman's research program, which encompasses many areas of synthetic organic chemistry, is suited for educating students at all levels: graduate students involved in research, undergraduates receiving training in the Birman lab, and those students taking Advanced Organic Lab under his supervision. In addition, Professor Birman's outreach activities in the public schools of Saint Louis are designed to spark the interest of elementary school students in science.
The overarching theme of the proposed project is the Lewis base-catalyzed enantioselective activation of thioesters. Specifically, the Birman group is developing an asymmetric catalytic rearrangement of alpha,beta-unsaturated thioesters into zwitterionic enolates, followed by a formal cycloaddition with pi-electrophiles. The resulting polycyclic structures, adorned with several stereocenters, are expected to be important in natural product synthesis and medicinal chemistry. These polycyclic products are difficult to access by other synthetic methods. In addition, the enantioselective alcoholysis of racemic thioesters is being explored, both in static and dynamic kinetic resolution mode. Amidine-based enantioselective acylation catalysts previously developed in the Birman laboratory are employed to achieve both of these new transformations. The educational plan associated with this research program includes further development of the organic chemistry component of the undergraduate curriculum at Washington University and continued outreach to elementary/middle school students in the public schools of Saint Louis.
