Ligand-promoted Enantioselective and Remote C-H Activation Reactions

配体促进的对映选择性和远程 C-H 激活反应

• 批准号: 8691885
• 负责人: Jin-Quan Yu
• 金额: $ 53.06万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8691885
• 关键词: Acids; Agonist; Amines; Amino Acids; Area; Biomedical Research; Carbon; Carboxylic Acids; Catalysis; Chemicals; Chemistry; Collaborations; Complex; Development; Disease; Distal; Drug Compounding; Electrons; Funding; Goals; Group Identifications; Hydrogen Bonding; Learning; Libraries; Ligands; Metals; Methods; Molecular; Mono-S; Non-Insulin-Dependent Diabetes Mellitus; Pharmaceutical Preparations; Pharmacologic Substance; Reaction; Research; Research Institute; Route; Serine Hydrolase; Site; Staging; Technology; Transition Elements; United States National Institutes of Health; Ursidae Family; activity-based protein profiling; carbene; design; drug candidate; frontier; human disease; infancy; inhibitor/antagonist; novel; pharmacophore; programs; public health relevance; receptor; scaffold; screening; success

DESCRIPTION (provided by applicant): Transition metal-catalyzed enantioselective sp3 C-H activation reactions can provide new synthetic routes for the expedient construction of bioactive molecules and drug compounds. Despite the great potential of such reactions, the development of enantioselective sp3 C-H functionalizations via an organometallic approach is in its infancy when compared to other more advanced methods of asymmetric catalysis. This proposal is centered on the development of novel enantioselective sp3 C-H activation reactions that would broaden the scope of transition metal-catalyzed asymmetric C-H functionalizations. The key strategy for achieving this goal is via the design and development of ligand scaffold that cooperates with the weak coordination between the substrate and the metal center to promote C-H activation. Additionally, we will relay our efforts through collaborations to biomedical research in identifying new drug candidates for the treatment of human diseases. Furthermore, we will strive to overcome the inherent need for the formation of 5-membered palladacycles in sp3 C-H activation to access remote methyl and methylene C-H bonds. Our key strategy is to design a template that relies on weak coordination to direct the metal towards the desired distal C-H bond. This approach would not only provide unprecedented access to a variety of ?- and ?-substituted aliphatic carboxylic acid derivatives, but also provide a platform for the late-stage diversification of drug molecules via functionalization of previously inaccessible remote C-H bonds.

描述（由申请人提供）：过渡金属催化的对映选择性SP3 C-H激活反应可以为生物活性分子和药物化合物的方便构建提供新的合成途径。尽管这种反应具有很大的潜力，但与其他更先进的不对称催化方法相比，通过有机金属方法的对映选择性SP3 C-H功能化的发展仍处于起步阶段。该建议集中在新型对映选择性SP3 C-H激活反应的发展，该反应将扩大过渡金属催化的不对称C-H功能化的范围。实现这一目标的关键策略是通过配体支架的设计和开发与底物和金属中心之间的弱协调合作以促进C-H激活。此外，我们将通过合作将我们的努力转移到生物医学研究中，以识别候选新药物治疗人类疾病。此外，我们将努力克服SP3 C-H激活中5元的Palladacycle的固有需求，以进入远程甲基和亚甲基C-H键。我们的关键策略是设计一个依赖弱协调的模板，将金属引导到所需的远端C-H键。这种方法不仅可以提供前所未有的访问？ 药物分子通过以前难以接近的远程C-H键的功能化多样化。