Dearomative Functionalization with Arenophiles

项目总结 芳香烃(芳烃)是一些最基本的原料化学品，生产 每年以百万吨的规模。这些化合物的化学转化在 在日常生活中；例如，在聚合物、涂料、农用化学品和药品的生产中。 脱芳构化反应将简单易得的芳烃转化为更具合成用途的不饱和芳烃 中间体。我们的长期目标是提供新的化学转化和战略，选择性地 引入功能性，从而极大地扩展了脱芳烃化学工具箱。 小的、含杂原子的复杂分子是生物(以及 药物和农用化学品)相关性，在药物化学中非常受欢迎，但它们也是 通常很难接近。芳香族化合物的选择性转化可以提供一条更直接的途径 这种理想的目标；然而，与脱芳烃官能化相关的许多挑战已经留下 这些类型的反应普遍不发达。拟议的研究致力于通过桥梁来满足这一需求 脱芳构化和烯烃化学之间的差距。从根本上说，这项提案的目标是获得 通过开发脱芳官能化来从简单芳香化合物中获得所需的结构基元 小分子--亲芳烃分子--能够使分离的烯烃在芳烃底物中发生反应。我们的预赛 结果表明，已建立的烯烃反应，如二羟基化和还原，现在可以 更直接地应用于芳烃。此外，亲芳烃与过渡金属催化作用相结合，可提供 独特的亲核取代反应活性底物，可以快速合成一种 各种氨基官能化脂环化合物。虽然许多已知的尝试将直接功能化 芳香族化合物会导致过度反应或分解，这种基于亲芳烃的策略允许选择性 和功能复杂性的受控引入。最后，这种方法提供的产品既是 通过现有方法合成具有挑战性，并与通过生物或 化学除芳香工艺。 总体而言，与芳香族的通用脱芳烃功能化平台的开发具有 通过提供对制药、农业和材料科学产生深远影响的潜力 从简单易得的芳烃中方便地获得具有定制性质的复杂小分子。

PROJECT SUMMARY Aromatic hydrocarbons (arenes) are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale. Chemical transformations of these compounds play a fundamental role in everyday life; for example, in the production of polymers, paints, agrochemicals, and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more synthetically useful unsaturated intermediates. Our long term goal is to provide new chemical transformations and strategies that will selectively introduce functionality and, consequently, greatly expand the dearomative chemical toolbox. Small, heteroatom-containing complex molecules are common motifs of biological (as well as pharmaceutical and agrochemical) relevance and are highly desired in medicinal chemistry, but they are also often difficult to access. Selective transformations of aromatic compounds could provide a more direct route to such desirable targets; however, the many challenges associated with dearomative functionalization have left these types of reactions widely underdeveloped. The proposed research strives to address this need by bridging the gap between dearomatization and alkene chemistry. Fundamentally, the goal of this proposal is to access desirable structural motifs from simple aromatic compounds by developing dearomative functionalizations using small molecules – arenophiles – that enable reactions of isolated alkenes in an arene substrate. Our preliminary results demonstrate that well-established olefin reactions, such as dihydroxylation and reduction can now be more directly applied to arenes. Additionally, arenophiles, in combination with transition metal catalysis, provide uniquely reactive substrates for nucleophilic substitution reactions, and could enable the rapid synthesis of a diverse range of aminofunctionalized alicyclic compounds. While many known attempts to directly functionalize aromatic compounds result in overreaction or decomposition, this arenophile-based strategy permits selective and controlled introduction of functional complexity. Finally, this approach provides products that are both challenging to synthesize via existing methods and complementary to those acquired through biological or chemical dearomative processes. Overall, the development of a general dearomative functionalization platform with arenophiles has the potential to make a profound impact on the pharmaceutical, agricultural, and materials sciences by providing expedient access to complex small molecules with tailored properties from simple and readily available arenes.