Combining Nickel and Photoredox Catalysis

Princeton University, Princeton NJ

Investigators

Linked publications & trials

Abstract

Abstract. A fundamental goal of our research program is the development of novel synthetic strategies that will allow for the efficient construction of medicinally useful compounds from simple, readily available starting materials. Along these lines, our group has dedicated significant effort to the application of photoredox catalysis to organic synthesis. This field of catalysis employs transition metal complexes or organic dyes which are capable of absorbing visible light. Absorption of a photon promotes a photocatalyst to a long-lived excited state, which may then act as an oxidant or a reductant via single-electron transfer. As such, photoredox catalysts harness visible light as a source of chemical energy, which can be used to overcome significant reaction barriers. Recently, our group and others have demonstrated that photoredox catalysis can be successfully merged with other catalytic platforms in order to capitalize on the strengths of each individual mode of catalysis. We have become particularly interested in exploring reactivity at the interface of photoredox catalysis and transition metal cross-coupling catalysis. In this research proposal, we outline new directions for our photoredox multicatalysis-based research program. The successful completion of the proposed aims will provide access to currently unknown or inaccessible reaction pathways and will allow common and usually ?benign? organic compounds to be activated as participants in cross-coupling reactions. In Aim I, we propose to develop an asymmetric decarboxylative cross-coupling via the merger of photoredox and nickel catalysis. In Aim II, we aim to harness the ability of nickel catalysts to activate alkyl halides to accomplish a direct sp3?sp3 cross-coupling. Aim III envisions the development of a nickel- and photoredox- catalyzed method for the conversion of esters into high-value scaffolds via CO2-extrusion- recombination. While Aims I?III focus on the cross-coupling of carboxylic acids, Aim IV proposes the introduction of a new class of readily available coupling partners by employing simple alcohol derivatives in nickel-photoredox cross-coupling. In Aim V, it is our objective to employ three discrete catalysts in order to accomplish C?H arylation of amines, ethers, and alcohols via hydrogen atom transfer and cross-coupling. Aim VI envisions the application of a related triple-catalytic strategy to develop a method for cross-electrophile coupling. In Aim VII, it is our goal to harness photocatalytic control of transition metal oxidation states in order to accomplish a nickel-mediated C?N coupling reaction. Finally, as part of a Diversity Supplement, Aim VIII proposes the construction of the polypyrroloindoline alkaloid isopsychotridine using iterative applications of a copper-catalyzed method developed in our laboratory.