Robust Photocatalytic Method Using Ethylene‐Bridged Flavinium Salts for the Aerobic Oxidation of Unactivated Benzylic Substrates

Abstract

7,8‐Dimethoxy‐3‐methyl‐1,10‐ethylenealloxazinium chloride (1a) was found to be a superior photooxidation catalyst among substituted ethylene‐bridged flavinium salts (R=7,8‐diMeO, 7,8‐OCH2O‐, 7,8‐diMe, H, 7,8‐diCl, 7‐CF3 and 8‐CF3). Selection was carried out based on structure vs catalytic activity and properties relationship investigations. Flavinium salt 1a proved to be robust enough for practical applications in benzylic oxidations/oxygenations, which was demonstrated using a series of substrates with high oxidation potential, i. e., 1‐phenylethanol, ethylbenzene, diphenylmethane and diphenylmethanol derivatives substituted with electron‐withdrawing groups (Cl or CF3). The unique capabilities of 1a can be attributed to its high photostability and participation via a relatively long‐lived singlet excited state, which was confirmed using spectroscopic studies, electrochemical measurements and TD‐DFT calculations. This allows the maximum use of the oxidation power of 1a, which is given by its singlet excited state reduction potential of +2.4 V. 7,8‐Dichloro‐3‐methyl‐1,10‐ethylenealloxazinium chloride (1 h) can be used as an alternative photocatalyst for even more difficult substrates.

Highly Chemoselective Catalytic Photooxidations by Using Solvent as a Sacrificial Electron Acceptor

“…Interestingly, unlike other flavin derivatives, only a weak triplet state, which is not quenched by the substrate, was observed by transient absorption spectroscopy for 3‐Cl (see Supporting Information S15). This may indicate that 3‐Cl participates in PET in its singlet excited state analogous to a similar ethylene‐bridged dimethoxyflavinium salt 1 a‐Cl (see Figure 1; R 3 =Me, R 7 =R 8 =OMe) [19a] . Neutral radical 3 ⋅ is formed via PET as monitored using steady‐state spectroscopy in the model reaction with trimethylamine.…”

“…We demonstrate the chemoselective approach using a riboflavin (vitamin B2) derivative because flavins, in general, are recognized as versatile photoredox catalysts. [8d,17,18] Among the flavin family (Figure 1), one can find very strong oxidizing agents such as salts 1-X (Figure 1A), which are characterized by excited state reduction potentials higher than + 2.5 V. [19] On the other hand, the photoexcited radical of deazaflavin 2 a (2 a *À ) has been shown to be one of the strongest reducing agents reported to date, as demonstrated by its highly negative oxidation potential (E ox * = À 3.3 V). [20] Aerobic benzylic photooxidation is the main area of application of the flavins.…”

Tuning riboflavin derivatives for photodynamic inactivation of pathogens

“…Flavins are also involved in the regulation of photochemical pathways due to strong blue light absorption, which results in the generation of highly oxidising excited states that can elicit biological signalling events or responses 5 – 8 . This photoexcitation process has been exploited in a number of photocatalytic applications, whereby modification of the flavin chromophore can enable the formation of high potential oxidative and reductive intermediates to afford useful synthetic methodology 9 – 11 .…”

Tuning Riboflavin Derivatives for Photodynamic Inactivation of Pathogens

“…[5][6][7][8] This photoexcitation process has been exploited in a number of photocatalytic applications, whereby modi cation of the avin chromophore can enable the formation of high potential oxidative and reductive intermediates to afford useful synthetic methodology. [9][10][11] Another application in which photoexcitation is utilised to generate reactive intermediates is within photodynamic inactivation (PDI) of pathogens. In this technique, a photosensitiser (PS) such as ribo avin, is employed to generate a burst of reactive oxygen species (ROS) in the vicinity of a particular pathogen in order to cause irreversible damage that leads to inactivation.…”