Novel Catalytic Annulation Chemistry

在这个由化学系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弗拉基米尔·格沃格扬教授正在开发新型过渡金属催化方法来合成多取代芳烃和杂芳烃。现有的催化方法对这些无处不在的类化合物遭受区域选择性的问题，而更有选择性的方法通常需要就业的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。为了解决这个问题，将追求开发用于选择性构建不同芳香族和杂芳香族框架的真正新颖的催化方法。拟议的工作预计将在健康相关领域产生更广泛的影响，通过提供新的有效途径，生物重要的中间体和材料科学，通过允许容易获得有价值的积木，可用于快速组装复杂的框架和共轭材料。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，通过显着减少废物和化学转化的成本。该项目的重点是扩大钯催化的[4+2]和正式的[2+2+2] benzannulation反应。重点介绍了新型活化基团的开发、迁移环化反应的研究以及C-H官能化技术在多取代苯合成中的应用。新的预benzannulation级联，涉及二聚的炔在一个头对头的方式，其次是他们的benzannulation与diynes也正在探索。 此外，开发新的后benzannulation级联，包括各种类型的顺序或一锅碳环化和杂环化后的benzannulation步骤正在进行。最后，几种新的杂苯成环模式被用于合成吡啶。这些新的反应，如果充分发展，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.