Multi-stated organic photocatalysts for sustainable molecular transformations

Current mainstream approaches for the chemical production of the active ingredients in the pharmaceutical and agrochemical industries utilize thermal energy to drive conventional ionic two-electron transfer events. Employment of other forms of energy can allow for development of new synthetic processes, thus resulting in a vast expansion of the chemical spaces. Our primary objectives in this research project are to use ubiquitous energy of visible light to create highly efficient catalytic processes driven by single-electron transfer (SET) and/or energy transfer (ET). Visible-light photocatalysis has advanced the state-of-the-art chemical synthesis via harnessing of mild energy visible light to productively drive various types of useful molecular transformations. Homogeneous photocatalysts such as ruthenium (Ru)/iridium (Ir)-based polypyridyl complexes or complex organic dyes can be excited under irradiation with visible light that will induce SET to/from organic substrates or ET via triplet-sensitization to provide reactive open-shell radical intermediates. However, there are several points that should be addressed to enable translation of these photocatalytic methods into more practical and sustainable chemical processes. First, rare transition metal-based photocatalysts such as Ru- and Ir-based ones are not suitable for sustainable chemical processes due to their cost and toxicity. Second, the irradiation of transition metal-based photocatalysts produces longer-lived triplet excited states that can induce outer-sphere SET or ET events with the substrates. However, the electronic excitation process is typically based on a metal-to-ligand charge-transfer (MLCT) band (commonly observed at 450-500 nm) so that only triplet excited states of lower energy (ET = nearly 45 kcal/mol = 2 eV) will be involved in the SET or ET events. The long-lived excited states are indispensable for intermolecular substrate activation processes via SET or ET, because the diffusion rate constant of molecules in solution are about 10*9-10 /s. Their redox windows, however, inevitably restrict their engagement in the redox processes of the readily available substrates having highly negative reduction potentials [such as organic halides and carbonyl compounds, E(red) = –2 V or less vs saturated calomel electrode (SCE)] as well as those with highly positive oxidation potentials (such as non-activated arenes and alkenes, E(ox) = 2 V or more vs SCE). On the other hand, to avoid the rarity and toxicity of transition metal-based photocatalysts, organic photosensitizers such as eosin Y, rhodamine 6G, acridinium salts and 10-phenyl-phenothiazine which have electron-donating and/or -withdrawing groups in pi-conjugated systems have been employed as photocatalysts. Since the lifetimes of their excited singlet states are generally shorter by ~1000-10000 times than the Ru/Ir-based photocatalysts, and the rate constants of the intersystem crossing (ISC) to the triplet state are about 10*6-7/s, the longer-lived triplet states cannot be employed effectively for the desired intermolecular chemical events. Based on these backgrounds, this research project will aim at rational design and development of novel chemically robust and versatile photosensitizers which display a wider redox potential windows, higher excitation energy and relatively longer-lived lifetime in their multiple photoexcited states to promote the desired SET/ET events under various reaction modes for the syntheses of a series of functionalized organic molecules that are relevant with pharmaceutical and agrochemical interests. Specifically, we would pursue the following topics as the major project milestones, which would be enabled by the synergy of the multidisciplinary expertise in the project team, spanning synthetic chemistry, and catalysis as well as electrochemistry and photochemistry: 1) Design and applications of novel multi-state organic photocatalysts (section 2.1). 2) Development of ketyl-aliphatic C-H cross coupling via SET-HAT relay catalysis (section 2.2). 3) Development of ET-SET relay catalysis for construction of macro/spirocycles (section 2.3). 4) Exploration of highly positive/negative electrochemical potentials via consecutive photoelectron transfer (section 2.4). 5) Novel catalysis scaffoldings for stereochemical control in radical coupling (section 2.5).