Dearomative Functionalization with Arenophiles

亲仁体的脱芳香功能化

基本信息

批准号：
10200084
负责人：
David Sarlah
金额：
$ 29.51万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2022-06-30
项目状态：
已结题

项目摘要

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.

项目概要芳香烃（芳烃）是一些最基本的原料化学品，其生产每年一百万吨规模，这些化合物的化学转化在其中发挥着重要作用。日常生活；例如聚合物、油漆、农用化学品和药品的生产。脱芳构化反应将简单、容易获得的芳烃转化为合成上更有用的不饱和化合物我们的长期目标是提供新的化学转化和策略，以选择性地进行。引入功能，从而极大地扩展了脱芳香化学工具箱。含有杂原子的小复杂分子是生物（以及药物和农用化学品）相关性，并且在药物化学中非常需要，但它们也通常难以获得的芳香族化合物的选择性转化可以提供更直接的途径。然而，与脱芳香功能化相关的许多挑战仍然存在这些类型的反应广泛欠发达。拟议的研究致力于通过桥接来满足这一需求。从根本上说，该提案的目标是获得脱芳构化和烯烃化学之间的差距。通过使用开发脱芳香功能化，从简单的芳香化合物中获得理想的结构基序我们的初步研究表明，小分子（亲芳烃）能够使分离的烯烃在芳烃底物中发生反应。结果表明，成熟的烯烃反应，例如二羟基化和还原现在可以此外，亲油剂与过渡金属催化相结合，可以更直接地应用于芳烃。用于亲核取代反应的独特反应底物，并且可以快速合成尽管许多已知的直接官能化的尝试，但仍存在多种氨基官能化的脂环族化合物。芳香族化合物会导致过度反应或分解，这种基于亲烯体的策略允许选择性最后，这种方法提供了两者兼而有之的产品。通过现有方法合成具有挑战性，并且与通过生物或方法获得的方法互补化学脱芳香过程。总体而言，与亲仁体一起开发通用的脱芳香功能化平台具有以下优势：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且容易获得的芳烃中方便地获得具有定制特性的复杂小分子。