Advances in (4+3)-Cycloaddition Chemistry

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In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Michael Harmata of the Department of Chemistry at the University of Missouri-Columbia will explore the development of methods for the generation of allylic cations under mild conditions and study their [4+3]-cycloadditions with dienes. Silyloxyacroleins will be prepared and treated with catalytic amounts of chiral Lewis acids in the presence of dienes. Such studies will also be conducted with vinylogs of these species. Chloroketones and various derivatives will be treated with chiral amine bases in the presence of dienes in anticipation of the generation of oxyallylic cations bonded to chiral counterions able to induce stereoselectivity in subsequent reactions. Silver salts of chiral non-nucleophilic anions will be used similarly, as will chiral thioureas with chloroketone derivatives. Finally, the photoionization of certain derivatives of allylic alcohols and the gold-catalyzed generation of allylic cations from selected esters of allylic alcohols will be developed. The [4+3]-cycloaddition reaction results directly in the synthesis of seven-membered rings, a substructure of a vast number of compounds that are biologically important. Further, studies from the Harmata group and others have demonstrated that this reaction can lead to a variety of ring sizes, increasing molecular complexity of simple starting materials in short order to produced value-added structures economically. The successful results of this work could positively impact the pharmaceutical, agrochemical and specialty chemical industries. In addition, this project will provide excellent training of students, including those from groups historically underrepresented in the sciences.