New Directions in Enantioselective C-H Functionalization

项目摘要 新的合成方法的发展有可能改变制药业 药物被制造，甚至什么类型的化合物将被设计为潜在的目标。的 合成的可及性是药物设计的关键组成部分， 战略开辟了可供考虑的潜在目标的新前景。这种转变 最近产生了相当大的兴趣是C-H官能化，因为它代表了一种不同的 如何将分子连接在一起的逻辑。其中一个主要的挑战是控制现场 在含有多个C-H键的底物中的选择性。一个有希望的方法是 铑催化的供体/受体卡宾反应，通过使用合适的催化剂，将 允许在伯、仲或叔C-H键上发生选择性反应。少校， 然而，与这种方法相关的限制是供体/受体卡宾的范围窄 主要限于衍生自乙烯基-芳基-和 杂芳基重氮乙酸酯。 该提案的重点是开发新型的供体/受体卡宾， 大大提高了这种有前途的方法的合成通用性，以获得新的化学品 空间这将通过扩大可与以下各项相关联的功能范围来实现： 给体/受体卡宾化学，设计了一类新的高对称性的碗状 手性催化剂，并说明了催化剂控制的C-H新的战略机遇 功能化应用于药学相关靶标。

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.