Research summary

Our group’s research is concerned with the development of efficient enantioselective and diastereoselective synthetic methods, and their application to the synthesis of drug molecules and natural products. We also carry out extensive mechanistic studies of our new reactions, principally through NMR spectroscopy (e.g. 31P NMR and 1H NMR), to gain mechanistic insight, identify intermediates, and establish general patterns of reactivity.  Much of our studies in recent years have involved the development of chiral organic nucleophile-catalyzed synthetic methods.  Specifically, we have developed a number of chiral phosphine-catalyzed reactions of ketenes providing versatile methods for the asymmetric synthesis of biologically important molecules such as β-lactones (ketene dimers and saturated β-lactones) and β-lactams.

In 2012, we disclosed the first catalytic asymmetric heterodimerization of ketenes. This reaction was catalyzed by an alkaloid nucleophile (a quinine or quinidine derivative) to give a β-lactone ketene heterodimer product. One current avenue of intense research in our lab involves elaboration of our ketene heterodimer products to cancer therapeutic agents and complex molecules isolated from mycobacterium tuberculosis.  We also have an interest in sulfur and phosphorus chemistry, as well as the development of new transition metal-catalyzed cross-coupling reactions.  In the area of sulfoxonium ylide chemistry, we published a modification of the Johnson-Corey-Chaykovsky reaction which facilitated a synthesis of gamma-lactones, through interception of a sulfoxonium ylide-derived betaine intermediate by a ketene molecule. This work has more recently led to us to investigate new reactions of vinyl sulfoxonium salts, providing routes to pharmaceutically important cyclic molecules.

Our group’s research in the US has been supported by the National Science Foundation (three awards: 2009-2012, 2012-2015, and 2015-2018) and by the National Institutes of Health (2014-2017).  Work on these and other new projects will continue at DCU in Ireland.