This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Reactions catalyzed by organic catalysts (amines, amino acids and amino alcohols) are often plagued by low reactivity (high catalyst loadings and long reaction times) and limited substrate scope. This project will investigate highly nucleophilic phosphines as organocatalysts in order to facilitate the design of new synthetic organic methodologies. Professor Kerrigan's group envisaged that phosphines would provide superior reactivity due to their enhanced polarizability at phosphorus relative to analogous nitrogen centered catalysts. As part of a program of studies towards the development of new organocatalyzed reactions involving phosphonium enolates, Professor Kerrigan's group has sought to develop an efficient methodology for the asymmetric dimerization of ketoketenes. While isolated examples of ketoketene dimerization have been reported in the past, no general system has emerged and, moreover, an asymmetric dimerization of ketoketenes has never been reported. This reaction will facilitate the study of the reaction of phosphines with ketenes, and furthermore provide a rare opportunity to study the reactivity of phosphonium enolate species. The synthetic utility of the proposed methodology will be validated through its application to the synthesis of interesting drug molecules (e.g. LY426965), and through the conversion of enantioenriched ketoketene dimers into useful chiral building blocks (e.g. 1,3-diketones, amino acids, and amino alcohols).
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Nessan J. Kerrigan of the Department of Chemistry at Oakland University. Professor Kerrigan's research efforts focus on the development of new phosphine-catalyzed reactions. The new methodologies arising from this project will provide access to chiral building blocks (intermediates) with great potential for the synthesis of complex molecules, and will enable alternative strategies for the construction of pharmacologically active molecules.
