Novel Catalytic Annulation Chemistry

在这个由化学部门化学合成项目资助的项目中，芝加哥伊利诺伊大学化学系的Vladimir Gevorgyan教授正在开发新的过渡金属催化方法来合成多取代芳烃和杂芳烃。现有的对这些普遍存在的化合物的催化方法存在区域选择性问题，而更有选择性的方法通常需要使用化学计量的有机金属试剂，这严重限制了这些方法的广泛应用。为了解决这一问题，将致力于开发真正新颖的催化方法来选择性地构建不同的芳香族和杂芳香族框架。拟议的工作预计将在与健康有关的领域产生更广泛的影响，因为它为获得具有重要生物学意义的中间体提供新的有效途径，并在材料科学领域产生更广泛的影响，因为它允许容易获得可用于快速组装复杂框架和共轭材料的有价值的构建块。此外，连续或一锅转化的发展，其中多个反应发生在一个烧瓶中，具有积极的环境影响，大大减少浪费和化学转化的成本。该项目的重点是拓宽pd催化的[4+2]和正式的[2+2+2]苄环反应。重点放在新的活化基团的发展，详细的迁移环化和碳氢功能化技术，以合成多取代苯。新的预苯环化级联反应，包括炔以头对头的方式二聚化，然后与双炔进行苯环化，也正在探索中。此外，新型苯并环化后级联反应的发展，包括在苯并环化步骤后进行的各种类型的顺序或一锅碳和杂环化反应。最后，介绍了几种新的杂苯环化方式用于合成吡啶。这些新的反应，如果完全发展，允许分子复杂性的急剧增加，使简单的前体容易获得重要的，密集取代的框架。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Vladimir Gevorgyan of the Department of Chemistry at the University of Illinois at Chicago is developing novel transition metal-catalyzed methodologies to synthesize multisubstituted aromatics and heteroaromatics. Existing catalytic approaches toward these ubiquitous classes of compounds suffer from regioselectivity problems, whereas more selective methods usually require employment of stoichiometric organometallic reagents, which severely limits broad application of these methodologies. To address this problem, development of truly novel catalytic methods for selective construction of diverse aromatic and heteroaromatic frameworks will be pursued. The proposed work is expected to have broader impacts in health related areas by providing new effective routes to biologically important intermediates and in material sciences by allowing easy access to valuable building blocks, which could be utilized in the rapid assembly of complex frameworks and conjugated materials. Moreover, the development of sequential or one-pot transformations, in which multiple reactions occur in one flask, has a positive environmental impact by dramatically reducing waste and the cost of chemical transformations.The project focuses on broadening Pd-catalyzed [4+2] and formal [2+2+2] benzannulation reactions. An emphasis is placed on the development of novel activating groups, elaboration of migratory cyclizations and C-H functionalization techniques to synthesize multisubstituted benzenes. Novel pre-benzannulation cascades, involving dimerization of alkynes in a head-to-head fashion, followed by their benzannulation with diynes is also being explored. In addition, the development of novel post-benzannulation cascades, including various types of sequential or one-pot carbo- and heterocyclizations proceeding after the benzannulation step is being pursued. Finally, several novel modes of heterobenzannulation are being used to synthesize pyridines. These novel reactions, if fully developed, allow for a dramatic increase of molecular complexity giving easy access to important, densely substituted frameworks from simple precursors.