Template Driven Access to Highly Congested Stereocenters: Synthetic and Mechanistic Studies

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Mukund Sibi from North Dakota State University, is studying new ways to synthesize crowded carbocyclic heterocyclic organic compounds (cyclic organic compounds containing heavy atoms such as N,O and S in addition to carbon) with control of stereochemistry. Heterocyclic building blocks with defined stereochemistries are valuable building blocks for natural product synthesis, chemical biology and medicinal chemistry.

For example, a majority of therapeutics used to treat human diseases contain heterocyclic substructures. On the other end of the spectrum, heterocycles are also integral in the manufacture of materials. The methods to be developed by Professor Sibi and his graduate students are designed to be efficient, cost effective, and eco-friendly.

The funding from the National Science Foundation will also make a significant impact on human capacity building by training graduate students to enter the 21st century workforce. Outreach activities are also part of this award. In the second year of the grant, ten faculty members from primarily undergraduate institutions will receive training on Introduction of DOSY (Diffusion Ordered Spectroscopy) a state-of-the-art method to study solution structure, enabling these faculty to takes such knowledge back to their respective institutions to teach students.

Another outreach activity of significance is a graduate course on heterocycles designed to engage students from multiple institutions where such courses are not offered.

Professor Sibi and his students are developing new methods for the installation of all carbon quaternary centers with control over relative and absolute stereochemistry. Reliable and catalytic methods for the construction of chiral quaternary centers are sparse. Current protocols to surmount this barrier are generally limited to a single reaction type.

The development of a strategy that performs across a broad class of reactions would deliver significant impact. In this work, Professor Sibi and co-workers will use an achiral-template-driven strategy to deliver reliable and effective solutions for the installation of hindered chiral centers by utilizing several important synthetic transformations. The intellectual merit of the work is focused on synthetic and mechanistic organic chemistry.

It will make fundamental advances in the preparation of small carbo- and heterocycles and develop mechanistic tools to understand the structure of the reactive intermediates involved in organic transformations. Broader impacts of the work are the development of new synthetic methodology for accessing carbo- and heterocycles as important tools for researchers in academia as well as the chemical industry.

The program offers a continuum of learning tools from basic to advanced, which will enable educating scientists across all levels in broad aspects of catalysis.

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.