A New Paradigm for Ether Synthesis

University Of Nebraska-Lincoln, Lincoln NE

Investigators

Abstract

Abstract In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Pat Dussault of the University of Nebraska-Lincoln and Prof. Keith Kuwata of Macalester College are developing new approaches to the synthesis of ethers. Ethers, which contain a Carbon-Oxygen-Carbon linkage, are an important functionality present in medicines, natural products, solvents, and organic materials. The research pursued under this award is anticipated to have impact both in chemistry and in associated fields such as drug discovery and materials science. Dussault and coworkers are also creating a practical and widely accessible knowledge clearinghouse related to the synthetic application of organic peroxides, that is encouraging wider exploitation and safer application of the rich chemistry of peroxides. Other broader impacts of this work include the training of both undergraduate and graduate students in experimental and computational research methods and the mutual enrichment of collaboration between a research university and a primarily undergraduate institution. Existing methods for the introduction of the ether group are predominantly based upon reaction of nucleophilic oxygen with electrophilic carbon. The research under this award employs both experimental and theoretical approaches to explore a new mode of synthesis based upon attack of carbon nucleophiles on the electrophilic oxygen atoms within organic peroxides. The research is organized around two major research aims. Aim 1 combines experimental and theoretical approaches to develop improved methods for ether synthesis by the reaction of peroxides with carbanions. Emphasis is placed on understanding the factors that influence peroxide reactivity, the mechanism of the bond-forming step, the scope of C-O bonds that are approachable via this strategy, and control of selectivity in attack on unsymmetrical peroxides. Aim 2 investigates intermolecular C-O bond forming reactions as an approach to specific classes of functionalized ethers and intramolecular reactions as an approach to cyclic and spirocyclic ethers.