Ligand-promoted Enantioselective and Remote C-H Activation Reactions

描述（由申请人提供）：过渡金属催化的对映选择性sp3 C-H活化反应可以为方便构建生物活性分子和药物化合物提供新的合成途径。尽管这些反应具有巨大的潜力，但与其他更先进的不对称催化方法相比，通过有机金属方法开发对映选择性sp3 C-H功能化尚处于起步阶段。该建议的重点是发展新的对映选择性sp3碳氢化合物活化反应，这将扩大过渡金属催化的不对称碳氢化合物功能化的范围。实现这一目标的关键策略是通过设计和开发配体支架，配合底物与金属中心之间的弱配合，促进C-H活化。此外，我们将通过合作将我们的努力传递给生物医学研究，以确定治疗人类疾病的新候选药物。此外，我们将努力克服在sp3 C-H活化过程中形成5元palladacycle的固有需求，以获得远程甲基和亚甲基C-H键。我们的关键策略是设计一种依赖弱配位的模板，将金属导向所需的远端碳氢键。这种方法不仅可以提供前所未有的各种γ-和δ-取代脂肪族羧酸衍生物，而且还可以通过以前无法获得的远程C-H键的功能化为药物分子的后期多样化提供平台。

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 γ- and δ-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.