Enantioselective Thiourea-Catalyzed C-H Functionalization via Hydride Transfer

描述（由申请人提供）：拟议的研究重点是通过分子内氧化还原反应开发硫脲催化的对映选择性C-H键功能化。阴离子结合催化是近年来发展起来的一种有机催化活化方式，它可能通过氢化物转移/C-C键形成序列提供一种实现不对称碳氢活化的有效手段。采用手性硫脲衍生物和强酸的组合，可以形成易于1,5-氢化物移位的阳离子中间体，并在随后的环化中形成环醚，环醚是许多天然产物中重要的结构基序。这种有机催化方法将提供一种有吸引力的替代过渡金属试剂，通常用于直接C-H功能化。详细的机理研究将有助于深入了解非共价相互作用控制成键事件的能力，这可能会影响未来的催化剂和反应设计。最后，所开发的方法将应用于生物相关化合物的合成，说明有机催化不对称C-H功能化在快速高效构建复杂有机结构方面的有效性。！

DESCRIPTION (provided by applicant): 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. !