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.
