Enantioselective Thiourea-Catalyzed C-H Functionalization via Hydride Transfer

通过氢化物转移对映选择性硫脲催化的 C-H 官能化

• 批准号: 8201867
• 负责人: David James Hardee
• 金额: $ 4.63万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8201867
• 关键词: Acids; Anions; Binding; Biological; Biological Factors; Catalysis; Complex; Cyclic Ethers; Cyclization; Development; Effectiveness; Event; Future; Health; Human; Hydrogen Bonding; Metals; Methodology; Methods; Oxidation-Reduction; Reaction; Reagent; Research; Structure; Thiourea; Transition Elements; base; biological systems; catalyst; computer studies; design; drug candidate; insight; research study; tool

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. !

描述（由申请人提供）：拟定研究的重点是通过分子内氧化还原反应开发对映选择性硫脲催化的C-H键官能化。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，它通过氢化物转移/C-C键形成过程实现C-H不对称活化。使用手性硫脲衍生物和强酸的组合应该能够形成易于发生1，5-氢化物位移的阳离子中间体，并随后进行环化，以对映选择性形成环醚，环醚是许多天然产物中的重要结构基序。这样的有机催化方法将提供一个有吸引力的替代过渡金属试剂经常采用直接C-H官能化。详细的机理研究将提供对非共价相互作用控制键形成事件的能力的深入了解，这可能会影响未来的催化剂和反应设计。最后，开发的方法将被应用到生物相关化合物的合成，说明有机催化的不对称C-H官能化的有效性，快速，高效地构建复杂的有机结构。! 公共卫生关系：所提出的C-H官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强有力的合成策略。可能的应用包括作为潜在候选药物或理解与人类健康相关的生物系统的工具的分子的合成。!