Photochemical Csp2–H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches

Abstract

Herein, we report an eco-friendly photochemical oxidative C sp 2 -H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K 2 S 2 O 8 , 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 E Ar 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.

Iodine pentoxide-mediated oxidative selenation and seleno/thiocyanation of electron-rich arenes

“…27 Nevertheless, there are only a few orthodox methods available for the selenocyanation of indoles using KSeCN as a selenocyating reagent with the aid of an oxidant 28 or visible light. 29 Thus, the reaction of indole 1a and KSeCN was carried out with 1.0 equiv. of I 2 O 5 as the reaction promoter in CH 3 CN at room temperature, and the expected 3-selenocyanoindole 6a was obtained with moderate yield.…”

Immobilized Rose Bengal as Photocatalyst for Metal‐Free Thiocyanation of Azaheterocycles under Continuous Flow Conditions

“…Flash chromatography was carried out on silica gel (230-400 mesh). Routine NMRs and 19 F-NMRs were recorded with a benchtop NMR, Spinsolve 80 ULTRA purchased from Magriteck. Characterizations were recorded with Brucker Avance 300 spectrometer, operating at 300 MHz for 1 H-NMR and 75 MHz for 13 C-NMR, witch complete proton decoupling.…”

“…[10] Thus, it should not be surprising that many original methodologies for generating CÀ SCN bonds involving nucleophilic substitution, electrophilic substitution or free-radical thiocyanation have recently been developed, [11] involving catalytic, [12] organocatalytic, [13][14][15] electrochemical [16] and photochemical [17,18] processes; some of them have been successfully investigated under continuous flow conditions. [19] Among them, photochemical induced thiocyanation reactions involving the use of air as oxidant (instead of stoichiometric oxidants) have recently attracted attentions, since these approaches show a reduced waste production and involve the use of photons to perform synthetic transformations. The first photoredox-catalyzed thiocyanation reaction was reported by Li and coworkers in 2014, in which indoles react with SCN radical generated by ammonium thiocyanate in the presence of Rose Bengal as organic dye upon irradiation with visible light and using air oxygen as oxidant.…”

Blue Light Irradiated Metal-, Oxidant-, and Base-Free Cross-Dehydrogenative Coupling of C(sp2)–H and N–H Bonds: Amination of Naphthoquinones with Amines

“…Consequently, an environmentally benign, green, and mild approach is highly desirable for C–N bond construction, which can afford densely substituted C2-aminated naphthoquinones and quinones. In recent decades, visible-light-driven photocatalyzed strategies have been developed, serving as a mild and powerful tool for carbon–carbon, − carbon–heteroatom, − and particularly C–N coupling reactions. − In 2016, MacMillan and co-workers reported photocatalyzed aryl amination using ligand-free Ni salt. The visible-light-mediated C 2 -amination of thiophenes with engineered amine substrates by using DDQ as an organo-photocatalyst has been achieved recently by Lei and co-workers .…”