Strongly Reducing Organic Photocatalysts as the "New Iridium" in Photoredox Catalysis

Colorado State University, Fort Collins CO

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Abstract

Project Summary The overarching objective of this Research Proposal is to establish dihydrophenazine, phenoxazine and carbazole derivatives as organic photocatalysts (O-PCs) for visible light photoredox catalysis in the formation of challenging covalent bonds vital to synthesis of medicinally relevant molecules. This O-PC platform will expand the synthetic capabilities of chemists for drug development to improve the wellbeing of the society. These O-PCs offer many advantages over commonly used noble-metal based PCs such as Ru(bpy)32+ and fac-Ir(ppy)3: they are generally cheaper, non-air and -moisture sensitive and less toxic in comparison to their noble metal counterparts. Preliminary data suggests that dihydrophenazine, phenoxazine and carbazole O-PCs possess a wide range of excited state reduction potential [E0* = E0(PC?+/3PC*)] and ground state oxidation potential [Eox = E0(PC?+/PC)]. In fact, the classes of dihydrophenazine and phenoxazine O-PCs are more powerful excited state reductants than Ru(bpy)32+ and fac-Ir(ppy)3. Thus, through computationally-guided catalyst design, these O-PCs can be designed to possess desired E0* and Eox, which will be used in various covalent bond coupling methodologies to access a diverse array of medicinally relevant molecules. Two specific aims have been tailored to achieve this overall goal. In Aim 1, a combined computational and experimental approach will be capitalized to realize classes of dihydrophenazine, phenoxazine and carbazole O-PC derivatives possessing a broad range of E0* and Eox. These O-PC families will provide organic and medicinal chemists the ability to match the E0* and Eox of the O-PC to the desired substrates in order to mediate selective bond activation and avoid potential side reactions. In Aim 2, tunable E0* and Eox of dihydrophenazine, phenoxazine and carbazole O-PCs will be exploited to forge challenging C-C, C-O, C-S, and C-N covalent bonds. These coupling reactions will introduce functionalities to medicinally relevant molecules such as pyridines, pyrroles, indoles and benzofurans. Realizing these two aims will convincingly demonstrate the applicability of dihydrophenazine, phenoxazine and carbazole O-PCs, thereby enabling the industrial-scale synthesis of medicinally relevant molecules through visible light photoredox catalysis.