Photochemical C_sp²-H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches

Herein, we report an eco-friendly photochemical oxidative C_sp²-H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K₂S₂O₈, which quickly oxidizes KSCN and KSeCN, finally producing arylthio/selenocyanates. Using this benign, atom-economic protocol, the desired chalcogenide products were obtained regioselectively, with isolated yields that range from very good to excellent. Although, mechanistic study indicates that it is difficult to distinguish between a radical to a S_EAr reaction mechanism between the photo-induced formed ^•SCN, for the former, or NCSSCN, for the latter, to the aromatic heterocycles. The inhibition experiment together with the observed reactivity and regioselectivity, would be in agreement with the latter. The synthetic methodology designed could be successfully adapted to continuous-flow systems in a segmented-flow regime, employing the organic phase as the product reservoir. Using this setup, the advantage of the latter can be demonstrated by reducing the reaction time and improving the product yields. Similarly, the scaling up of the reaction to gram scale resulted in favorable outcomes by the flow setup, which installs the photo-flow chemistry as a powerful tool to be included into routine reaction procedures, which have great relevance for the pharmaceutical industry.