Catalytic, Regioselective C-H Activation/Oxidation of Substituted Arenes

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The goal of the proposed project is to develop new catalysts and methodology for the regioselective oxidation of aromatic C-H bonds. Initially the project will focus on developing catalysts for the selective meta oxidation of 1,3-disubstituted arenes; the long-term objective is to expand the scope of the reaction to include more diverse substrate classes. Substituted arenes are ubiquitous in pharmaceutical targets, therefore the ability to selectively functionalize the traditionally uncreactive C-H bonds in arenes will provide a very efficient way to access these biologically active molecules. We propose that regioselective oxidation reactions will arise from the development of catalysts that selectively activate the least hindered aromatic C-H bond present in the arene substrate. In the case of 1,3- disubstituted arenes, we hypothesize that steric interactions between the proposed catalysts and substituents on the aromatic ring will lead to selective functionalization of the least hindered meta position, rather than at the electronically favored ortho or para positions. Palladium(ll) N-heterocyclic carbene complexes, which introduce very bulky substituents in close proximity to the coordination sphere of palladium, are proposed for a system which utilizes phenyliodosyl acetate to selectively introduce acetoxy groups . Reports on highly regioselective rhodium (III) catalyzed reactions have also led us to propose the development of new methodology for the rhodium-catalyzed acetoxylation of substituted arenes. Finally, the insight gained in the development of methods for the selective oxygenation of aromatic C-H bonds will be applied in the development of systems for the selective carboxylation of aromatic C-H bonds. Prior reports have shown that the non-selective, catalytic acetoxylation and carboxylation reactions proceed by very similar pathways. Hence, it is expected that catalysts which are active and selective in acetoxylation reactions will also be active and selective for the carboxylation of the least hindered C-H bonds in substituted arenes. Relevance to Public Health Upon successful completion of the proposed research project we will provide chemists with new methods to synthesize substituted arenes, molecules that are commonly found in Pharmaceuticals. The reactions we will develop will be a very efficient way of making these compounds, and will improve the ways that pharmaceutical compounds are produced. [unreadable] [unreadable] [unreadable]