Development of New Aryne Chemistry

通过化学系化学合成项目资助的该奖项，伊利诺伊大学芝加哥分校的李大成教授探索了一种新的合成方法，该方法是从形成非传统的应变芳香族中间体中发展出来的。 该方法在合成具有生物活性的天然产物、药物、药品和其它含有芳香亚结构的功能材料方面具有许多应用。反应发现，其效用和一般范围的探索，以及天然和医学相关化合物的合成应用，为学生提供了一个有效的研究平台，使学生具备成为劳动力中有竞争力的研究人员的知识和技能。重要的是，因为大多数学生通过这些研究领域的培训，预计将在学术界或工业环境中追求的职业生涯，他们的贡献将从基础科学到人类health.This研究开拓了一种方法，直接从无环多炔前体反应性arynes的形成。这些芳炔及其以非常规方式生成的同系物的有利反应性允许其随后的官能化经历Alder烯反应、亲核加成、氢卤化和卤代烷基化。在过渡金属催化剂的存在下，这些芳炔还可以促进烷基上未活化的C-H键的有效官能化，这可以进一步扩展到芳族体系，提供正式的氢化芳基化。这些芳炔基转换的反应性配置文件和机制进一步研究基于DFT的理论计算。芳炔反应性的这些新的方面，结合机械的理解，提供了一种替代方法的限制，目前的方法涉及1，2-消除官能化的苯衍生物。通过从非芳族前体直接构建芳炔，发展了一种多功能的新合成工具，用于合成各种官能化的芳族系统，包括吲哚、二氢吲哚、咔唑和许多其他芳族结构。

Through this award funded by the Chemical Synthesis Program of the Division of Chemistry, Prof. Daesung Lee of the University of Illinois at Chicago explores a new synthetic method evolved from the formation of an unconventional strained aromatic intermediate. This method has many applications for the synthesis of biologically active natural products, pharmaceuticals, drugs, and other functional materials containing aromatic substructures. The reaction discovery, exploration of its utility and general scope, and application to the synthesis of natural and medicinally relevant compounds, provides an effective research platform for equipping students with the knowledge and skills to become competitive researchers in the work force. Importantly, because most students trained through these research areas are expected to pursue careers in either academia or industrial settings, their contributions will range from basic science to human health.This research exploits a method for the formation of reactive arynes directly from acyclic multiyne precursors. The favorable reactivity of these arynes and their congeners generated in unconventional manners allows their subsequent functionalization to undergo Alder-ene reactions, nucleophilic addition, hydrohalogenation, and haloalkylation. In the presence of transition metal catalysts, these arynes also can promote an efficient functionalization of unactivated C-H bonds on alkyl groups, which can be further extended to aromatic systems, providing a formal hydroarylation. The reactivity profiles and mechanisms of these aryne-based transformations are further investigated by DFT-based theoretical calculations. These new aspects of aryne reactivity, in combination with a mechanistic understanding, provide an alternative approach to the limitations of current methods involving 1,2-elimination of functionalized benzene derivatives. Through the direct construction of arynes from non-aromatic precursors, a versatile new synthetic tool is evolved for the synthesis of various functionalized aromatic systems, including indoles, indolines, carbazoles, and many other aromatic structures.