Methods for Selective Functionalization of (Hetero)arene Rings

项目摘要 该项目旨在解决芳烃去功能化过程中的众多挑战，从而达到高度装饰 芳香环，大多数药物的关键成分。目前，将芳烃功能化的方法有多个 位置需要迭代的耦合反应。芳烃的官能化提供了一种有吸引力的策略 将多个官能团结合到芳环中。不幸的是，这些反应受到了 由于多步合成、反应范围有限和位置不佳而导致访问起始材料的问题 芳烃中三键的两个可能位置的选择性。 我们小组的目标是通过使用过渡金属催化来扩大 芳烃去功能化的范围和用途。我们计划使用c1对称配体来控制 芳烃加成官能团的区域选择性。此外，通过引入过渡金属， 使用以前从未在催化中使用的新芳烃前体进行催化，我们将允许访问 以前由于环紧张而无法接触到的芳纶环。过渡金属催化剂将能够结合 到达芳纶，缓解环紧张。最后，提出了一系列新的去功能化反应。 这些新反应包括F、N和CF3基团的添加，这是因为它们在医学上的重要性 化学反应。 如果这项提议的目标实现，我们预计这种化学反应将提供容易的途径 种类繁多的高官能化芳烃环。这些将提供重要的基石和机会 用于医学相关分子的后期功能化。

Project Summary This project aims to solve numerous challenges in aryne difunctionalization en route to highly decorated arene rings, critical components of most pharmaceuticals. Currently, methods to functionalize arenes in multiple positions require iterative coupling reactions. Difunctionalization of arynes provides an attractive strategy to incorporate multiple functional groups into an arene ring. Unfortunately, these reactions are plagued with problems with accessing starting materials due to multistep syntheses, limited reaction scope, and poor site selectivity for the two possible positions of the triple bond in an aryne. Our group aims to overcome all of these challenges by using transition metal catalysis to expand the scope and utility of aryne difunctionalization. We plan to use C1 symmetric ligands in order to control regioselectivity of the functional group addition to the aryne. Additionally, by the introduction of transition metal catalysis with new aryne precursors that have previously never been used in catalysis, we will allow access to aryne rings that were previously inaccessible due to ring strain. The transition metal catalyst will be able to bind to the aryne and relieve ring strain. Finally, a wide variety of new difunctionalization reactions are proposed. These new reactions encompass additions of F, N, and CF3 groups due to their importance in medicinal chemistry. If the goals of this proposal are achieved, we anticipate that this chemistry will provide easy access to a wide variety of highly functionalized arene rings. These will provide important building blocks and opportunities for late stage functionalization of medically relevant molecules.