Visible Light Photoredox Catalytic α-Cyanation Reactions of Tertiary Amines

Visible-light photoredox catalysis, a novel and green catalytic strategy, has recently received increasing attention from chemists and been widely applied to organic synthesis in the past years. This catalytic strategy enables the generation of various reactive species under mild conditions without stoichiometric activation reagents and shows its significance for sustainable chemistry. alpha-Amino nitriles are highly versatile intermediates having extensive applications in organic synthesis and biological transformation. The oxidation of tertiary amines using stoichiometric oxidants followed by the nucleophilic addition reaction of the iminium intermediate by cyanide ion (CN-) represents a direct approach for their synthesis. However, the use of stoichiometric oxidants and the production of huge amounts of hazardous waste (i.e., CN-) is undesirable from environmental viewpoints. Here, we report a photoredox catalytic alpha-cyanation reaction of tertiary amines using cyanobenziodoxol as a stable and safe cyanide source. This protocol is favored for mild conditions, the avoidance of extra oxidant and highly toxic cyano anion, good functional tolerance as well as safe and simple operations. By doing so, a variety of alpha-amino nitriles are afforded in good to excellent yields. A sunlight-driven reaction and a gram-scale reaction further demonstrate the utility of this methodology. In addition, we also succeed to apply the same strategy to the decarboxylative cyanation of carboxylic acids, affording the nitriles in moderate yields. A possible mechanism was proposed on the basis of known literature and our previous reports. The representative procedure for the alpha-cyanation reaction of tertiary amines is as following: N-phenyl piperidine la (0.48 mmol), cyanobenziodoxol 2a (0.40 mmol), photocatalyst Ir[dF(CF3)PPy](2)(dtbbpy)PF6 (0.008 mmol) and CsHCO3 (0.60 mmol) were dissolved in DCM (8 mL). Then, the resulting mixture was degassed via 'freeze-pump-thaw' procedure (3 times). After that, the solution was stirred at a distance of ca. 5cm from a 7 W blue LEDs (450 similar to 460 nm) at room temperature for 16 h. Upon completion, the crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate 30 : 1 similar to 10 : 1) directly to give the desired product. The procedure for the decarboxylative cyanation of carboxylic acids is similar.