Photoredox Catalysis Unlocks the Nickel-Catalyzed Cyanation of Aryl Halides under Benign Conditions

Abstract

The transition-metal-catalyzed cyanations of aryl halides are among the most used methods for synthesizing aryl nitriles. Despite tremendous advances, cyanating an aryl halide in a facile and benign fashion has generally been unsuccessful. The challenge for this significant transformation is the strong affinity of cyanide for metal centers, which makes organometallic catalysis elusive by hampering oxidative addition and reductive elimination. Herein, we demonstrate for the first time that photoredox/nickel-catalyzed cyanations of aryl halides are readily enabled by visible light, in which Ni(II) species are transiently oxidized to Ni(III) species, thereby facilitating the subsequent cyanide transfer and reductive elimination. Using this dual catalysis strategy, we cyanated aryl and alkenyl halides at room temperature in a highly benign manner (30 examples, 53-93% yields) by avoiding the use of air-sensitive ligands, Ni(0) processors, and hypertoxic cyanation reagents, while also not generating excess metal waste. Computational studies were also used to help understand the present transformation.

Photochemically Enabled, Ni-Catalyzed Cyanation of Aryl Halides

“…While elegant Ni­(II) precatalysts that catalyzed reductive cyanation of aryl electrophiles have been devised to address these problems, the scope is limited, especially for aryl chlorides (Scheme , 1). During the preparation of this work, photoredox Ni-catalyzed cyanation of aryl halides has been reported, affording a condition-benign alternative . However, expensive iridium photocatalysts were used, and their scope is limited to (hetero)­aryl bromides and activated aryl chlorides (Scheme , 2).…”

Nickel‐Catalyzed Reductive Coupling of Vinyl Triflates and 1,4‐Dicyanobenzene to Access Alkenyl Nitriles

“…Transition metal‐catalyzed C−CN bond formation offers an alternative approach for their preparation. Inorganic cyanide salts [8] (e. g., KCN, NaCN, Zn(CN) 2 , K 4 [Fe(CN) 6 ], CuCN), TMSCN, [9] cyanohydrin, [10] butyronitrile, [11] tert ‐butyl isocyanide, [12] α‐aminoacetonitriles, [13] N ‐cyano‐ N ‐phenyl‐ p ‐toluenesulfonamide (NCTS), [14] 4‐cyanopyridine N ‐oxide, [2c] MeNO 2 [15] and azides [16] are the major nitrile sources. However, the hazard from the inorganic waste, toxicity from the in‐situ generated HCN, and explosive risk pose environmental sustainability issues.…”

Photoinduced Nickel-Catalyzed Demethylative Cyanation and Decarboxylative Cyanomethylation of Aryl Halides

“…Alternatively, transition-metal-catalyzed cyanation reactions of aryl electrophiles with diverse cyanide sources, including KCN, NaCN, Zn­(CN) 2 , and TMSCN, have been developed, providing efficient ways for the generation of aryl nitriles. − However, the high toxicity or low solubility of these cyanating reagents, as well as the catalyst deactivation caused by the strong interaction between the cyanide anion and the metal center, made safer and readily available cyano sources highly desirable. In this regard, elegant reactions via palladium or nickel-catalyzed cyanations of aryl halides using different types of organic cyanating reagents such as cyanohydrin, alkylnitrile, , MPMN, 4-cyanopyridine N -oxide, α-aminoacetonitrile, and 1,4-DCB have been reported. Although the employment of these organic cyanating sources provides better solutions for the introduction of cyanomotif into arenes, the use of excess metal reductant, air-sensitive additives, presynthesized cyanating reagents, strong bases, as well as high temperature and operating complexity still remain the drawbacks (Figure b).…”

“…9−23 However, the high toxicity or low solubility of these cyanating reagents, as well as the catalyst deactivation caused by the strong interaction between the cyanide anion and the metal center, made safer and readily available cyano sources highly desirable. In this regard, elegant reactions via palladium or nickel-catalyzed cyanations of aryl halides using different types of organic cyanating reagents such as cyanohydrin, 24 alkylnitrile, 25,26 MPMN, 27 4-cyanopyridine N-oxide, 28 α-aminoacetonitrile, 29 and 1,4-DCB 30 sources provides better solutions for the introduction of cyanomotif into arenes, the use of excess metal reductant, airsensitive additives, presynthesized cyanating reagents, strong bases, as well as high temperature and operating complexity still remain the drawbacks (Figure 1b). On the other hand, the cyanomethylation of aryl halides is among the most important transformations to access α-aryl nitriles.…”

“…The subsequent oxidative addition of an aryl halide results in the Ni III intermediate C. Concurrently, bromoacetonitrile 2 reacts with i Pr 2 NH to in situ generate the compound i Pr 2 N(CH 2 CN) D, which undergoes ligand exchange to transfer the CN group to Ni III . 29 The reductive elimination at Ni III intermediate E yields the cyanation product and regenerates Ni I intermediate B (Figure 3a). For the cyanomethylation reaction, the photocatalyst radical cation oxidizes Cs-salt 4 to produce radical species F, which is 47 to complete the catalytic cycle (Figure 3b).…”