Photocatalysis in Aqueous Micellar Media Enables Divergent C–H Arylation andN-Dealkylation of Benzamides

Abstract

Photocatalysis in aqueous micellar media has recently opened wide avenues to activate strong carbon−halide bonds. So far, however, it has mainly explored strongly reducing conditions, restricting the available chemical space to radical or anionic reactivity. Here, we demonstrate a controllable, photocatalytic strategy that channels the reaction of chlorinated benzamides via either a radical or a cationic pathway, enabling a chemodivergent C−H arylation or N-dealkylation. The catalytic system operates under mild conditions with methylene blue as a photocatalyst and blue LEDs as the light source. Factors determining the reactivity of substrates, their selectivity, and preliminary mechanistic studies are presented.

Light‐Induced Dealkylation of Benzamides in Aqueous Solution

“…[21] In the context of amide N-dealkylation, our group developed a photocatalytic, bluelight induced method for modification of N-alkylbenzamides in aqueous micellar solutions (Figure 1a). [22] This strategy, however, requires the presence of a halide substituent at o-position to the amide group, whose role is to make the molecule susceptible to reductive activation. A more direct approach was proposed by Lu and co-workers, who targeted secondary benzamides in the presence of oxone, catalytic amount of KBr and under white LEDs irradiation.…”

“…Recently, light‐induced processes gained traction as sustainable methods for exploring radical or radical‐polar crossover reactions under mild conditions [21] . In the context of amide N ‐dealkylation, our group developed a photocatalytic, blue‐light induced method for modification of N ‐alkylbenzamides in aqueous micellar solutions (Figure 1a) [22] . This strategy, however, requires the presence of a halide substituent at o ‐position to the amide group, whose role is to make the molecule susceptible to reductive activation.…”

N-Heterocyclic Nitreniums Can Be Employed as Photoredox Catalysts for the Single-Electron Reduction of Aryl Halides

“…The former can reduce aryl iodide, affording the desired aryl radical. According to known reports, the generated aryl radical would undergo 1,5-HAT, intramolecular cyclization, SET, and deprotonation processes, yielding the final product. In the cases of NHN A4 and A5 , because the OTf – and BF 4 – cannot serve as electron donors, we proposed that TMEDA could serve as an electron donor to form the CTC with NHN at least to initiate the reaction (Figure , path B).…”

“…To validate the feasibility of our strategy to reduce aryl halides, we first examined whether NHN salts could promote the cascade reaction of 2-iodo- N , N -diisopropylbenzamide 1 under blue light irradiation . The exploration of the transformation led us to identify optimal experimental conditions for the efficient activation of aryl iodide with NHN salts (Scheme ).…”

Photoredox aerobic oxidation of unreactive amine derivatives through LMCT excitation of copper dichloride

“…In sharp contrast to the impressive achievements with amines, N -demethylations of amides are largely underexplored to date because of the inertness of amides. 8 In 2015, Cho et al described a C–N bond cleavage of N -benzylamides through visible light photocatalysis. 8 c Very recently, a Cu-catalyzed N -demethylation of amides using N -fluorobenzenesulfonimide as an oxidant was reported by Zhang's group.…”