Mechanistic Investigation of Photoinduced, Copper-Catalyzed Cross-Coupling Reactions

California Institute Of Technology, Pasadena CA

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Abstract

? DESCRIPTION (provided by applicant): Photocatalysis and transition metal-catalyzed cross-couplings are integral in the development of new methods for the synthesis of biologically relevant molecules; however, to date little overlap exists between the two fields. A general photoinduced copper-catalyzed cross-coupling methodology developed by the Peters and Fu labs has demonstrated that irradiation of a copper catalyst in the presence of an aryl or alkyl halide and pronucleophile leads to a variety of carbon-heteroatom bonds, linkages that are invaluable in constructing pharmacophores. Despite the broad scope and utility of these conditions, the mechanisms by which these reactions proceed remain unclear. A mechanistic understanding of these catalytic processes would provide guidance in expanding the scope of the reaction and identifying catalyst deactivation pathways. A comprehensive mechanistic investigation will be undertaken to gain insight into the coupling of thiols and amides to aryl halides using mechanistic model copper complexes. Optical spectroscopy, electron paramagnetic resonance, and fluorimetry will be employed to identify putative intermediates and monitor potential elementary steps. Furthermore, access to laser facilities at the Beckman Institute Laser Resource center will permit observation of transient species and in-depth analysis of the photophysical processes that render copper-nucleophiles potent photoreductants and platforms for bond-formation.