Thiourea-Catalyzed Nucleophilic Desymmetrization of Meso-Cyclopropanes

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DESCRIPTION (provided by applicant): Asymmetric catalysis provides necessary synthetic tools for the synthesis of enantiomerically pure, biologically active molecules. The field of asymmetric catalysis has been dominated by the use of transition metal complexes. The use of transition metal catalyzed reactions poses grave concerns for the chemical and pharmaceutical industry. Great care must be taken in purification and disposal practices associated with the use of transition metal catalysts, as many of these complexes are toxic. To develop alternatives to these practices, chemists have turned to nature for inspiration in the development of more efficient, selective, and environmentally benign catalysts for useful organic transformations. With an increase in the understanding of the mechanisms behind enzyme function, interest has erupted over the last decade in the use of organic molecules as catalysts for asymmetric organic transformations. The absence of metals at the active site of many enzymes demonstrates the ability of non-metallic functional groups to serve as catalytic centers. Chemists are attempting to mimic these non-metallic active sites with small organic compounds. This proposal outlines the development of stereoselective 1,5-functionalization of carbonyls through thiourea catalyzed desymmetrizations of meso-cyclopropanes by nucleophilic ring opening. Current synthetic methodologies allow for the facile construction of meso-cyclopropanes and their desymmetrization would give rise to complex chiral scaffold. The bifunctional nature of the thiourea catalysts should result in simultaneous activation of the cyclopropane as well as the nucleophile. The goal of this research is to develop thiourea compounds as catalysts for this transformation.