Development of New Aryne Chemistry

伊利诺伊大学芝加哥分校的Daesung Lee教授通过化学系化学合成项目资助的这一奖项，探索了一种新的合成方法，这种方法是从非常规的紧张芳香中间体的形成演变而来的。该方法在合成具有生物活性的天然产物、药物、药物和其他含有芳香亚结构的功能材料方面具有广泛的应用。反应的发现，探索其效用和一般范围，并将其应用于天然和药物相关化合物的合成，为学生提供了一个有效的研究平台，使他们具备知识和技能，成为有竞争力的研究人员。重要的是，由于通过这些研究领域培训的大多数学生预计将在学术界或工业环境中从事职业，他们的贡献将从基础科学到人类健康。本研究开发了一种由无环多炔前体直接生成反应性芳烃的方法。这些芳烃及其以非常规方式生成的同系物的良好反应性使其随后的官能化可以进行醛烯反应、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，这些芳烃还可以促进烷基上未活化的C-H键的有效功能化，这可以进一步扩展到芳香体系，提供正式的氢化芳基化。通过基于dft的理论计算，进一步研究了这些炔基转化的反应性分布和机理。芳烃反应性的这些新方面，结合对机理的理解，提供了一种替代方法，以克服目前涉及1,2-消除官能化苯衍生物的方法的局限性。通过从非芳香族前体直接构建芳香族，一种多功能的新合成工具被开发出来，用于合成各种功能化芳香体系，包括吲哚、吲哚、咔唑和许多其他芳香结构。

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.