The proposed research is focused on the development of enantioselective thiourea-catalyzed C-H bond functionalization via intramolecular redox reactions. Anion-binding catalysis, a recently developed organocatalytic mode of activation, may provide an effective means to achieve asymmetric C-H activation through a hydride transfer/C-C bond formation sequence. Employing combinations of chiral thiourea derivatives and strong acids should allow the formation of cationic intermediates prone to a 1,5-hydride shift and subsequent cyclization for the enantioselective formation of cyclic ethers, important structural motifs in many natural products. Such an organocatalytic method would provide an attractive alternative to the transition metal reagents often employed in direct C-H functionalization. Detailed mechanistic studies would provide insight into the ability of non-covalent interactions to control bond-forming events, potentially impacting future catalyst and reaction design. Finally the developed methodology would be applied to the synthesis of biologically relevant compounds, illustrating the effectiveness of organocatalytic asymmetric C-H functionalization for the rapid and efficient construction of complex organic structures. !
The proposed C-H functionalization methodology will provide a powerful synthetic strategy for the rapid and efficient construction of organic compounds that have biological activity. Possible applications include the synthesis of molecules that are potential drug candidates or tools for understanding biological systems related to human health. !