In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Nessan J. Kerrigan of the Department of Chemistry at Oakland University will explore the development of the catalytic asymmetric ketene heterodimerization reaction and its applications. While catalytic homodimerizations of ketenes have received some attention over the last twenty years, ketene heterodimerization has remained a very underdeveloped reaction, despite its great potential. Problems associated with the thermal ketene heterodimerization reaction include poor ketene heterodimer regioselectivity, competing ketene homodimerization, low ketene heterodimer yields, and absence of asymmetric variants. Professor Kerrigan's group will investigate a stepwise mechanistic approach, promoted by a chiral alkaloid organocatalyst under mild conditions, rather than a (concerted) thermal cycloaddition approach, in order to facilitate a regioselective and enantioselective heterodimerization reaction. Some applications of the methodology toward the synthesis of biologically active molecules will be investigated and aldol reactions of ketene heterodimer-derived metal enolates will also be evaluated.
This work could lead to more efficient and flexible access to building blocks useful for the preparation of an array of structurally complex and biologically active molecules. Such chemistry will contribute to green synthesis as the proposed ketene heterodimerization methodology avoids the use of metal catalysts. Successful development of the methodology will have an impact on the pharmaceutical and chemical industries, as it will provide ready and inexpensive access to a number of desirable building blocks for complex molecule construction. This project will provide excellent training of students, ranging from undergraduate to post-doctoral levels, including those from groups historically underrepresented in the sciences.
