New Directions in Enantioselective C-H Functionalization

项目摘要 新合成方法的发展有可能改变制药的方式 药物被制造出来，甚至什么类型的化合物将被设计为潜在的目标。这个 合成可及性是药物设计中的关键组成部分，而全新的合成 战略为考虑潜在目标开辟了新的前景。一种转变，它具有 最近产生了相当大的兴趣是C-H功能化，因为它代表了一种不同的 关于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网站 在含有多个C-H键的底物中的选择性。一种很有前途的方法是 给体卡宾和受体卡宾的反应，如果使用合适的催化剂，将会 允许选择性反应发生在一级、二级或三级C-H键上。一位少校， 然而，这种方法的局限性是供体/受体卡宾的范围很窄。 目前使用的，主要限于从乙烯基芳基衍生的卡宾 杂芳基重氮乙酸酯。 这项提议的重点是开发新型的供体/受体卡宾，这将 极大地增强了这一有希望的方法的合成通用性，以获得新的化学物质 太空。这将通过扩展可关联的功能范围来实现 施主/受主卡宾化学，设计了一类新型的高对称性碗形化合物 手性催化剂，并展示了催化剂控制的C-H的新战略机遇 功能化适用于与药物相关的靶标。

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.