Enantioselective Thiourea-Catalyzed C-H Functionalization via Hydride Transfer

描述(由申请人提供)：建议的研究重点是通过分子内氧化还原反应来开发硫脲催化的C-H键功能化。阴离子结合催化是最近发展起来的一种有机催化活化方式，它可以通过氢化物转移/C-C键的形成序列来实现不对称的C-H活化。使用手性硫脲衍生物和强酸的组合应该允许阳离子中间体的形成，容易发生1，5-氢化物移动和随后的环化反应，从而形成环醚的对映选择性形成，环醚是许多天然产物中重要的结构基元。这种有机催化方法将为直接C-H官能化中常用的过渡金属试剂提供一种有吸引力的替代方法。详细的机理研究将提供对非共价相互作用控制成键事件的能力的洞察，这可能会影响未来的催化剂和反应设计。最后将所开发的方法应用于生物相关化合物的合成，展示了有机催化不对称C-H官能化在快速高效构建复杂有机结构方面的有效性。好了！ 与公共健康相关：拟议的C-H功能化方法将为快速有效地构建具有生物活性的有机化合物提供一个强大的合成策略。可能的应用包括合成潜在的候选药物分子或了解与人类健康有关的生物系统的工具。好了！

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. ! PUBLIC HEALTH RELEVANCE: 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. !