Cyano Source Research Articles

Nucleophilic Cyanation of Enones and Imines with Formamide as the Cyano Source

AbstractA convenient cyano source for the nucleophilic 1,4‐addition to enones and 1,2‐addition to imines has been developed, by generating the cyano unit in situ. via the TCT‐assisted dehydration of formamide. This protocol distinguishes itself by transition‐metal/ligand free conditions, compatibility with 1,4‐/1,2‐addition, readily available substrates and versatile synthetic utilities of the cyanated products.

Palladium-Catalyzed Denitrative Synthesis of Aryl Nitriles from Nitroarenes and Organocyanides.

A denitrative cyanation of nitroarenes using organocyanides and a palladium catalyst was developed. The key for this reaction was the utilization of an aminoacetonitrile as a cyano source to avoid the generation of stoichiometric metal- and halogen-containing chemical waste. A wide range of nitroarenes, including heteroarenes and pharmaceutical molecules, can be converted into aryl nitriles.

Palladium-Catalyzed Directed Carbon-Carbon Bond Activation of Aryl Nitriles for Cyano Transfer.

Herein, we report the C-H cyanation of indoles via a palladium-catalyzed directed C-CN activation reaction using aryl nitrile as a cyano source. The employment of the phenoxy-oriented group is the key to the cleavage of the C-CN bond. This protocol features a broad substrate scope, good efficiency, and high regioselectivity. Furthermore, the practical application of this protocol was showcased in the late-stage functionalization and synthesis of indole derivatives, which were derived from drugs and natural products, through the process of cyanation.

Ni-Catalyzed Cyanation of (Hetero)aryl Halides with Acetonitrile as Cyano Source

Ni-Catalyzed Cyanation of (Hetero)aryl Halides with Acetonitrile as Cyano Source

Nickel-catalyzed asymmetric reductive arylcyanation of alkenes with acetonitrile as the cyano source

Chiral 3-cyanomethyl oxindoles were synthesized in high enantioselectivities and yields. The employment of acetonitrile as a cyano source via Zn(OTf)2-assisted β-carbon elimination is distinct from the common cyanation reaction modes.

A facile one-pot synthesis of N-acyl-1-cyano-1,2,3,4-tetrahydroisoquinoline via a photoredox and Reissert-type reaction from 1,2,3,4-tetrahydroisoquinolines

This work reports a protocol for the direct α-cyanation/N-acylation of 1,2,3,4-tetrahydroisoquinolines via a one-pot photoredox and Reissert-type reaction using air as the oxidant and acyl cyanide as acyl and cyano source at ambient temperature.

Synthesis of cyano-substituted γ-lactams through a copper-catalyzed cascade cyclization/cyanation reaction.

A convenient copper-catalyzed cascade cyclization/cyanation reaction for the construction of cyano-containing γ-lactams was developed. The protocol employed TMSCN as the cyano source and proceeded in water under simple conditions. Mechanistic studies indicated this reaction involved an amidyl radical initiated cascade 5-exo-trig cyclization/cyanation process. It is capable of generating a series of cyano-substituted γ-lactams and relative 2-oxazolidinone derivatives with a broad substrate scope.

Recent Advances on Radical-Mediated Cyanoalkylation/Cyanation using AIBN and Analogues as the Radical Sources

AbstractAIBN (2,2′-azobisisobutyronitrile) and analogues are readily available chemical reagents that are widely used as free-radical initiators of polymer chemistry. Importantly, AIBN and derivatives are also safe and efficient (alkyl)cyano sources for synthesizing cyano-containing scaffolds. In the past decades, synthetic strategies using AIBN and derivatives as radical sources have attracted increasing attention from the synthetic community. This review will provide a valuable tool for understanding the importance of AIBN and derivatives in the area of synthetic chemistry. In this context, we present a comprehensive review that guides readers through the developments in AIBN chemistry over the past five years from several aspects.1 Introduction2 Radical Addition onto Alkenes or Alkynes using AIBN as Cyanoalkyl Radical3 Dehydrogenated, decarboxylated cyano-alkylation by using AIBN and analogues4 Synthesis of Ketone and its Derivatives with AIBN and Analogues as Carbonyl Source5 Construction of Multi-ring Skeletons in the Presence of AIBN and Analogues6 Direct Application as Cyano (CN) Source in Cyanation Reactions7 Conclusions

Copper‐Catalyzed Cyanation of Aryl Iodides with Formamide as the Cyano Source

AbstractA practical and convenient protocol for copper‐catalyzed cyanation of aryl iodides with formamide as the cyano source was developed, providing various aryl nitriles in good to excellent yields under ligand and base free conditions. Compared to the reported cyanation reactions of aryl halides with formamide at high temperature (130–145 °C), lower reaction temperature (100 °C) and excellent substrate compatibility make this method more attractive in synthetic and pharmaceutical chemistry.

Ni‐Catalyzed Cyanation of Allylic Alcohols with Formamide as the Cyano Source

AbstractFormamide as the safe cyano source! A Ni‐catalyzed cyanation of unactivated allylic alcohols and formamide to provide various α,β‐unsaturated nitriles was developed by generating the cyano unit in situ from safe and readily available formamide.

Palladium-Catalyzed Cyanation of Arenediazonium Tetrafluoroborate Derivatives with 2-(Piperidin-1-yl)acetonitrile as the Cyano Source

AbstractThe present study describes the one-pot palladium-catalyzed cyanation of commercially available aryldiazonium tetrafluoroborate derivatives with 2-(piperidin-1-yl)acetonitrile (an organic cyano reagent) under mild conditions. This process utilizes a Pd/(Me3Si)2 system and is applied to a wide scope of aromatic diazonium substrates to give the corresponding nitrile-containing products in moderate to high yields (59–92%). This methodology is employed for the preparation of etravirine, a drug used for the treatment of HIV, and for transformations of 1H-indole-2-carbonitrile into compounds that are used as a NMDA receptor antagonists and that have high potential against mutant HIV strains. The mechanism proposed for this Pd-catalyzed cyanation involves cyanide ions, as confirmed using indicator paper.

Ru(III)-catalyzed construction of variously substituted quinolines from 2-aminoaromatic aldehydes (ketones) and isoxazoles: Isoxazoles as cyclization reagent and cyano sources

A Ru(Ⅲ)-catalyzed annulation reaction of 2-aminoaromatic aldehydes (ketones) and isoxazoles to afford diverse 3-cyanoquinolines has been developed. Notably, isoxazole acted as a cyclization reagent and nontoxic cyano source via N-O bond cleavage and fragmentation. Variously substituted (especially 6- or 7-substituted) quinolines could be easily afforded. This procedure features wide functional group compatibility, efficiency and avoiding toxic cyano source. Meanwhile, this protocol could be successfully applied to scale-up synthesis. Further chemical transformations of 3-cyanoquinoline could give some valuable skeletons, demonstrating its potential in synthetic application

Copper-mediated Regioselective C–H Cyanation of Phenols with Assistance of Bipyridine-type Bidentate Auxiliary

Abstract A Cu-mediated ortho-selective C–H cyanation of phenols with ethyl cyanoformate as the cyano source has been developed. The key to success is the introduction of 4,4′-di-tert-butyl-2,2′-bipyridine (dtbpy) bidentate auxiliary on the phenol oxygen, which is easily attachable, detachable, and recyclable. The newly developed protocol is tolerant of several carbonyl functional groups, which are incompatible with previous Lewis-acid-promoted cyanation of phenols.

Site-Selective Electrochemical C-H Cyanation of Indoles.

An electrochemical approach for the site-selective C-H cyanation of indoles employing readily available TMSCN as cyano source has been developed. The electrosynthesis relies on the tris(4-bromophenyl)amine as a redox catalyst, which achieves better yield and regioselectivity. A variety of C2- and C3-cyanated indoles were obtained in satisfactory yields. The reactions are conducted in a simple undivided cell at room temperature and obviate the need for transition-metal reagent and chemical oxidant.

Electrochemical Oxidative C−H Cyanation of Quinoxalin‐2(1H)‐ones with TMSCN

AbstractBoth quinoxalin‐2(1H)‐ones and nitriles are valuable organic compounds, and it is an interesting task to introduce cyano into quinoxalin‐2(1H)‐ones. Herein a regioselective C−H cyanation of quinoxalin‐2(1H)‐ones was developed with a nucleophilic cyano source TMSCN under electrochemical oxidative conditions. This process allowed the synthesis of C3 cyanated quinoxalin‐2(1H)‐ones in moderate to excellent yields in the absence of transition‐metal catalysts and organic hydroperoxides.

Copper-catalyzed synthesis of CN-containing chroman-4-ones via intramolecular radical cascade acyl-cyanation reaction

A copper-catalyzed intramolecular radical cascade acyl-cyanation to synthesize cyano-containing chroman-4-ones has been developed. A series of CN-substituted chroman-4-one derivatives can be prepared with moderate to good yields using green cyano source under mild conditions. Control experiments indicated this reaction involved an intramolecular acyl radical addition/cyanation process. Moreover, this protocol features step- and atom-economy, and the introduction of cyano group into the chroman-4-one is of great interest and importance.

Electrochemical Oxidative Regioselective C-H Cyanation of Imidazo[1,2-a]pyridines.

Electrochemical oxidative regioselective C-H cyanation of imidazo[1,2-a]pyridines was developed using readily available TMSCN as the cyano source. The KH2PO4/K2HPO4 buffer was essential for this transformation. This protocol was compatible with a broad range of substituted imidazo[1,2-a]pyridines and provided the C3 cyanated products in moderate to excellent yields.

Retraction notice to “Metal-catalyzed cyanation of aromatic hydrocarbon with less toxic nitriles as a cyano source” [Tetrahedron 76/40 (2020) 131388

Retraction notice to “Metal-catalyzed cyanation of aromatic hydrocarbon with less toxic nitriles as a cyano source” [Tetrahedron 76/40 (2020) 131388

Nickel/Cobalt‐Catalyzed Reductive Hydrocyanation of Alkynes with Formamide as the Cyano Source, Dehydrant, Reductant, and Solvent

AbstractA Ni/Co co‐catalyzed reductive hydrocyanation of various alkynes was developed for the production of saturated nitriles. Hydrocyanic acid is generated in situ from safe and readily available formamide. Formamide played multiple roles as a cyano source, dehydrant, and reductant for the NiII pre‐catalyst and vinyl nitriles, along with acting as the co‐solvent in this reaction. Detailed mechanistic investigation supported a pathway via hydrocyanation of C≡C bond and the subsequent reduction of C=C bond. Wide substrate scope, the employment of a cheap and stable nickel salt as pre‐catalyst, a safe cyano source and convenient experimental operation render this hydrocyanation practical for the laboratory synthesis of saturated nitriles.magnified image

Metal-mediated C-CN Bond Activation in Organic Synthesis.

Nitriles are ubiquitous versatile building blocks in organic synthesis. Common reactions of nitriles include the transformation of cyano groups into carbonyl and amine moieties. The functionalization of nitriles can also be accomplished at the alpha-position of alkanenitriles and at the ortho-position of cyanoarenes. On the other hand, the C-CN bond of nitriles has rarely been recognized as a valuable reaction site due to its thermodynamic robustness. Although it has been known for a long time in organometallic chemistry that C-CN bonds can be cleaved by transition-metal complexes, this elemental reaction had not been used in catalytic synthetic transformations of nitriles until two decades ago. This review surveys the progress of metal-catalyzed reactions of nitriles via C-CN bond activation. After introducing several different modes to activate C-CN bonds by various transition metals, catalytic reactions are categorized mainly into two parts: (i) reactions with CN as a leaving group and (ii) reactions with nitriles as a source of CN groups. Cross-coupling-type transformations with a cyano leaving group, cyanation reactions using nitriles as a nontoxic cyano source, and novel synthetic reactions such as carbocyanation are highlighted together with useful demonstrations of their utility in organic synthesis.