Inverting Coupling Selectivity with Cooperative Metal-Ligand Constructs

项目总结/摘要 催化科学和技术的进步使得能够制备用于 治疗人类疾病。催化交叉偶联反应是最常用的反应之一， 用于制药工业中药物和候选药物的组装。芳基醚和氟- 在合成中，离子交换物是常见的中间体，但它们仍然被认为是具有挑战性的亲电试剂 用于催化交叉偶联。催化方法使这类亲电体能够交叉偶联， 允许它们的选择性功能化将显著有助于生物活性小分子的制备， 克里斯该探索性研究项目的目标是开发一种新的强键交流技术， 活化，这将使广泛的进展，催化交叉偶联反应的非柠檬酸底物。 第一个重要的里程碑将是建立芳基C-O和C-F键的化学计量活化 跨金属-配体协同构建体，并实现这些亲电体的催化交叉偶联。 第二个重要的里程碑将是实现C-O和C-F底物的选择性活化， 存在其它可官能化部分。这项研究有望产生新的实用价值。 用于构建药理学相关的小分子的催化方法， 选择性合成的原理。同时，该研究也为催化偶联技术的发展提供了新的思路 基于金属配体结构作为键合的协同功能引擎的概念化， 制造和破坏综合起来，这些成果将改变催化强债券的做法 通过在均相催化中引入一种新的和强有力的方式来活化。

PROJECT SUMMARY/ABSTRACT Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to treat human disease. Catalytic cross coupling reactions are among the most commonly employed reac- tions for the assembly of drugs and drug candidates in the pharmaceutical industry. Aryl ethers and fluo- rides are common intermediates in synthesis, but they are still considered to be challenging electrophiles for catalytic cross coupling. Catalytic methods that open this class of electrophile to cross coupling and allow their selective functionalization would significantly aid in the preparation of bioactive small mole- cules. This exploratory research project has the goal of developing a new technology for strong bond ac- tivation that will enable broad advances in catalytic cross coupling reactions of recalcitrant substrates. The first major milestone will be to establish the stoichiometric activation of aryl C–O and C–F bonds across metal-ligand cooperative constructs and to realize catalytic cross coupling of these electrophiles. The second major milestone will be to achieve selective activation of C–O and C–F substrates in the presence of other functionalizable moieties. The proposed research is expected to yield new practical catalytic methods for the construction of pharmacologically-relevant small molecules that meet the chal- lenges of selective synthesis. Also, the research will establish a new technology for catalytic coupling based on the conceptualization of metal-ligand constructs as cooperative functional engines for bond making and breaking. Taken together, these outcomes will transform the practice of catalytic strong bond activation by the introduction of a new and powerful modality in homogeneous catalysis.