Investigation of Masked Acyl Cyanides in Organocatalyzed Reactions

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Julie Pigza of the University of Southern Mississippi (USM) is studying the use of chiral and achiral squaramide organocatalysts to deliver a masked acyl cyanide (MAC) reagent at an increased oxidation state which can be revealed at a later stage. The continual development of new catalytic reactions is a vital research area that enables the synthesis of chiral building blocks which impacts wide-ranging industries including agriculture, pharmaceutical development, and energy resources. Organocatalysis uses catalysts derived from carbon sources, requires no precious metals such as gold, palladium or silver, and continues to be at the forefront of sustainability. Key to the success of organocatalyzed reactions are the non-bonding interactions that organize the catalyst and substrate in the most optimal way to ultimately determine bond formation. In this proposal, the Pigza research group will investigate the use of MAC reagents through an interdisciplinary approach of organic synthesis, organocatalysis, and computational chemistry. The proposed research will train high school, community college, undergraduate, and graduate students in the Gulf South region to be competitive in the STEM workforce. To expand the impact of this project beyond the research laboratory, high-impact activities will be implemented in undergraduate teaching laboratories at USM and nearby community colleges to expose students to the scientific method. Students will obtain hands-on authentic research experiences through the modular synthesis of organocatalysts while also visualizing molecular structures and properties using a web-based computational program. With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Julie Pigza of the University of Southern Mississippi is studying reversal of polarity strategies utilizing umpolung reagents to result in the formation of unnatural bond disconnections. This strategy will incorporate chiral bifunctional organocatalysts that activate substrates through various modes of noncovalent interactions that ultimately promote stereoselection. Masked acyl cyanides (MAC) are umpolung reagents that are uniquely suited to stereoselective bond-forming processes enabled by organocatalysts. This project will enable new amidation and carboxylation methods, ubiquitous functional groups found throughout biologically active molecules. An increased fundamental understanding of the ensemble of noncovalent interactions between a catalyst and substrate required to achieve high stereoselection will be achieved through a synergistic approach that combines laboratory synthesis and computational chemistry. Central to the research program is a student-centered model where students will be effectively trained in both synthetic and computational methods, providing them with the skills to be more innovative and competitive in STEM fields. To broaden the impact beyond the Pigza research group, this project will foster connections with community college faculty through the development of a toolkit of authentic research-driven laboratory reactions to recruit students into science fields. Computational chemistry software to study abstract atomic and molecular phenomena will also be introduced into undergraduate teaching laboratories as a tool to retain students in STEM disciplines. 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.