CAREER: Development of Stereoselective Cu-Catalyzed Reductive Coupling Reactions

Virginia Commonwealth University, Richmond VA

Investigators

Abstract

With the support of the Chemical Catalysis program in the Division of Chemistry, Joshua Sieber of the Department of Chemistry at Virginia Commonwealth University (VCU) will investigate and develop new chemical tools to synthesize amine-derived polar organic compounds. These compounds are prevalent in nature, and the pharmaceutical industry uses and develops them to study biological processes and create new therapeutics for the treatment of human diseases. However, such compounds are often extremely difficult to access and synthesize. The goals of this research are to develop new synthetic tools to enable easy access to these important amine-derived organic compounds using earth-abundant copper metal-based catalyst systems. Studies will also be performed to understand how these processes work so that the efficiency of these new techniques can be continually improved. The educational objective of this CAREER proposal aims to recruit and prepare a diverse STEM (Science, Technology, Engineering and Mathematics) workforce for careers at the frontiers of the chemical sciences through hands-on training of the scientific method using the framework of synthetic organic chemistry. This goal will be achieved through: 1) introducing Richmond Public High School students to careers in synthetic organic chemistry through interactive classroom visits and opportunities to perform scientific research in the principal investigator’s laboratory in the summer, and 2) developing a new undergraduate advanced organic chemistry laboratory at VCU aimed at providing synthesis skills to students for applications to industrial careers in chemistry. Development of synthetic methodology to enable the construction of C–C bonds is at the core of organic chemistry. Having a “toolbox” of C–C bond-forming reactions enables the synthetic chemist to access many molecular organic targets desired for applications in chemical biology, medicinal chemistry and materials science. This proposal aims to develop new stereoselective and regiodivergent Cu-catalyzed processes to introduce multiple heteroatom-groups in the final product in a single reaction step to allow for convenient and straightforward access to chiral poly(heteroatom)-containing compounds. The core of the investigation will consist of the study of allenamides in asymmetric Cu-catalyzed reductive coupling reactions with aldehyde and imine electrophiles. Development of these processes is expected to: 1) improve the synthetic efficiency for the preparation of molecular architectures that are difficult to prepare by other techniques; 2) allow for the conversion of basic feedstocks to a wide range of enantio-enriched chiral building blocks of significance in natural product synthesis, chemical biology and chiral catalyst design, and 3) provide mechanistic insights to aid in the future development of general, stereoselective catalytic umpolung (polarity-reversed) processes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.