New Directions in Enantioselective C-H Functionalization

对映选择性 C-H 官能化的新方向

• 批准号: 10121603
• 负责人: HUW M DAVIES
• 金额: $ 35.68万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10121603
• 关键词: Chemicals; Chemistry; Complement component C4a; Complex; Development; Drug Design; Ensure; Generations; Goals; Hydrogen Bonding; Ligands; Logic; Methodology; Methods; Modification; Pharmaceutical Preparations; Pharmacologic Substance; Protocols documentation; Reaction; Reporting; Rhodium; Scheme; Site; Structure; carbene; catalyst; design; diazo compound; interest; novel; phosphonate; scaffold

Project Summary The development of new synthetic methods has the potential to transform how pharmaceutical drugs are made and even what types of compounds will be designed as potential targets. The synthetic accessibility is a crucial component in the design of drugs and entirely new synthetic strategies open up new vistas of potential targets for consideration. A transformation that has generated considerable recent interest is C-H functionalization, because it represents a different logic for how to join molecules together. One of the major challenges is to control the site selectivity in substrates containing multiple C-H bonds. A promising approach has been the rhodium-catalyzed reactions of donor/acceptor carbenes, which by using the right catalyst, will allow selective reactions to occur at either primary, secondary of tertiary C-H bonds. A major, limitation associated with this approach, however, is the narrow range of donor/acceptor carbenes that are currently used, primarily limited to carbenes derived from vinyl- aryl- and heteroaryldiazoacetates. This proposal focuses on the development of new types of donor/acceptor carbenes, which will greatly enhance the synthetic versatility of this promising methodology to access new chemical space. This will be achieved by expanding the range of functionality that can be associated with the donor/acceptor carbene chemistry, designing a new class of high symmetry bowl-shaped chiral catalysts, and illustrating new strategic opportunities for catalyst-controlled C-H functionalization applied to pharmaceutically relevant targets.

项目概要 新合成方法的开发有可能改变制药方式 药物的制造，甚至什么类型的化合物将被设计为潜在的目标。这 合成可及性是药物设计和全新合成的关键组成部分 战略开辟了可供考虑的潜在目标的新前景。一个转变有 C-H 功能化最近引起了相当大的兴趣，因为它代表了一种不同的 如何将分子连接在一起的逻辑。主要挑战之一是控制站点 含有多个 C-H 键的底物的选择性。一种有前途的方法是 铑催化的供体/受体卡宾反应，通过使用正确的催化剂，将 允许选择性反应发生在伯键、仲键或叔C-H键上。一个专业， 然而，与这种方法相关的局限性是供体/受体卡宾的范围狭窄 目前使用的卡宾主要限于衍生自乙烯基-芳基-和 杂芳基重氮乙酸酯。 该提案重点关注新型供体/受体卡宾的开发，这将 大大增强了这种有前景的方法的合成多功能性，以获取新的化学品 空间。这将通过扩展可关联的功能范围来实现 供体/受体卡宾化学，设计一类新型高对称性碗形 手性催化剂，并阐明催化剂控制的C-H的新战略机遇 应用于药学相关目标的功能化。