Novel Catalytic Annulation Chemistry

在这个由化学系化学合成计划资助的项目中，伊利诺伊大学芝加哥分校化学系的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。对于这些无处不在的化合物，现有的催化方法存在区域选择性问题，而更具选择性的方法通常需要使用化学计量比的有机金属试剂，这严重限制了这些方法的广泛应用。为了解决这个问题，将继续开发真正新颖的催化方法来选择性地构建各种芳香族和杂芳族骨架。这项拟议的工作预计将在健康相关领域产生更广泛的影响，为生物重要中间体和材料科学提供新的有效途径，使人们能够方便地获得可用于快速组装复杂框架和结合材料的有价值的构件。此外，在一个烧瓶中发生多个反应的连续或一锅转化的发展，通过显著减少废物和化学转化的成本，对环境产生了积极的影响。该项目侧重于扩大Pd催化的[4+2]和形式[2+2+2]苯环反应。重点介绍了合成多取代苯类化合物的新活化基团的开发、迁移环化反应和C-H官能化技术。还在探索新颖的苯环化前级联，包括以头对头的方式进行炔烃的二聚化，然后将其与二炔进行苯环化。此外，正在开发新的苯环化后级联反应，包括在苯环化步骤之后进行的各种类型的顺序或一锅碳环化和杂环化反应。最后，几种新的杂苯环化方式正被用于合成吡啶。这些新颖的反应，如果完全开发，允许分子复杂性的急剧增加，从而很容易从简单的前体获得重要的、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.