Methods for Selective Functionalization of (Hetero)arene Rings

项目摘要 该项目旨在解决芳炔双官能化过程中的众多挑战，以高度装饰 芳烃环是大多数药物的关键成分目前，多种芳烃官能化的方法 位置需要反复的偶联反应。二官能化的arynes提供了一个有吸引力的策略， 将多个官能团引入芳烃环中。不幸的是，这些反应受到 由于多步合成、有限的反应范围和不良的场地， 芳炔中三键的两个可能位置的选择性。 我们小组的目标是克服所有这些挑战，通过使用过渡金属催化剂来扩大 芳炔双官能化的范围和效用。我们计划使用C1对称配体来控制 官能团加成到芳炔上的区域选择性。此外，通过引入过渡金属， 催化与新的芳炔前体，以前从未用于催化，我们将允许获得 芳炔环，以前由于环应变而不可接近。过渡金属催化剂将能够结合 芳炔并减轻环张力。最后，提出了各种新的双官能化反应。 这些新的反应包括添加F、N和CF3基团，因为它们在药物中的重要性。 化学. 如果这一提议的目标得以实现，我们预计这种化学反应将提供一种容易获得的方法， 各种高度官能化的芳烃环。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.