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Cyanations

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Various electron-rich aromatics could be smoothly converted into the corresponding aromatic nitriles in good yields by treatment with POCl₃ and DMF, followed by molecular iodine in aqueous ammonia. The present reaction is a novel metal-free one-pot method for the preparation of aromatic nitriles from electron-rich aromatics.
S. Ushijima, H. Togo, Synlett, 2010, 1067-1070.

The commercially available, bench-stable dimethylmalononitrile (DMMN) enables an electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates.
J. T. Reeves, C. A. Malapit, F. G. Buono, K. P. Sidhu, M. A. Marsini, C. A. Sader, K. R. Fandrick, C. A. Busacca, C. H. Senanayake, J. Am. Chem. Soc., 2015, 137, 9481-9488.

Visible light promotes a Ni-catalyzed cyanation of aryl halides with 1,4-dicyanobenzene as a cyanating agent. A broad array of aryl bromides, chlorides, and druglike molecules could be converted into their corresponding nitriles.
Y. Yan, J. Sun, G. Li, L. Yang, W. Zhang, R. Cao, C. Wang, J. Xiao, D. Xue, Org. Lett., 2022, 24, 2271-2275.

A t-Bu₃P-monoligated Pd catalyst in MeCN-THF enabled an efficient general aromatic cyanation reaction under practicable conditions using NaCN as cyanide source, low-boiling recyclable solvents, and minimal quantities of inexpensive, nontoxic promoters. The reaction converts aromatic bromides to the corresponding nitriles in very good yield in short reaction time and tolerates many functional groups.
A. V. Ushkov, V. V. Grushin, J. Am. Chem. Soc., 2011, 133, 10999-11005.

In the presence of a highly effective Pd/CM-phos catalyst, an efficient cyanation of aryl chlorides proceeds at 70°C in general. Common functional groups such as keto, aldehyde, ester, nitrile and -NH₂, and heterocyclic coupling partners are well tolerated. Moreover, a sterically hindered nonactivated ortho,ortho-disubstituted electrophile is shown to be a feasible coupling partner in cyanation.
P. Y. Yeung, C. M. So, C. P. Lau, F. Y. Kwong, Org. Lett., 2011, 13, 648-651.

A Ni-catalyzed reductive coupling enables the synthesis of benzonitriles in good yields from aryl (pseudo)halides and 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions.
L. R. Mills, J. M. Graham, P. Patel, S. A. L. Rousseaux, J. Am. Chem. Soc., 2019, 141, 19257-19262.

Aryl and vinyl nitriles have been prepared in very high yields from the corresponding bromides using palladium-catalyzed reactions under microwave irradiation. Furthermore, flash heating was used successfully for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions. One-pot transformation of aryl halides directly to the aryl tetrazoles could also be accomplished.
M. Alterman, A. Hallberg, J. Org. Chem., 2000, 65, 7984-7989.

In the palladium-catalyzed cyanation of aryl bromides utilizing the air-stable XantPhos-PdCl₂ precatalyst, DIPEA as a reducing agent generates the active Pd(0) species in situ. Twenty-two substituted benzonitriles have been synthesized.
J. R. Coombs, K. J. Fraunhoffer, E. M. Simmons, J. M. Stevens, S. R. Wisniewski, Miao Yu, J. Org. Chem., 2017, 82, 7040-7044.

A mild and efficient, palladium-catalyzed reaction allows the cyanation of a wide range of (hetero)aryl halides and triflates at low catalyst loadings with mild temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor.
D. T. Cohen, S. L. Buchwald, Org. Lett., 2015, 17, 202-205.

A nickel-catalyzed cyanation of (hetero)aryl halides uses readily available and inexpensive Ni(dppf)Cl₂ as a precatalyst, a substoichiometric amount of Zn(CN)₂, and DABAL-Me₃ as as a soluble reductant. Addition of catalytic tetrabutylammonium bromide (TBABr) is beneficial, due to facilitating dissolution of low levels of the cyanide salt.
G. Duran-Camacho, J. C. Hethcox, Org. Lett., 2022, 24, 8397-8400.

A general catalyzed cyanation of hetero(aryl) chlorides using less toxic Zn(CN)₂ as the cyanide source relies on the use of inexpensive NiCl₂·6H₂O/dppf/Zn as the catalytic system and DMAP as additive. The cyanation occurs under mild reaction conditions with wide functional group tolerance. The method was also successfully extended to aryl bromides and aryl iodides.
X. Zhang, A. Xia, H. Chen, Y. Liu, Org. Lett., 2017, 19, 2118-2121.

Hemilabile, bulky, and electron-rich MOP-type ligands enable a highly efficient palladium-catalyzed cyanation of unactivated aryl chlorides and even aryl mesylates with potassium hexacyanoferrate in good yields using t-BuOH and H₂O as the solvent and K₂CO₃ as the base.
Y. Tu, Y. Zhang, S. Xu, Z. Zhang, X. Xie, Synlett, 2014, 25, 2938-2942.

A trans-spanned palladium complex has efficiently and selectively catalyzed the cyanation of aryl halides. The suggested reaction conditions are mild, exhibit good scope of substrates, and circumvent the need for an inert atmosphere and amine co-ligands.
O. Grossman, D. Gelman, Org. Lett., 2006, 8, 1189-1191.

K₄[Fe(CN)₆] (a nontoxic cyanide source) allows in combination with 0.1 mol % Pd(OAc)₂ a practical, ligand-free cyanation of aryl bromides in good to excellent yields.
S. A. Weissman, D. Zewge, C. Chen, J. Org. Chem., 2005, 70, 1508-1510.

A copper iodide mediated cyanation of arylboronic acids and aryl iodides with ethyl (ethoxymethylene)cyanoacetate as cyanating agent involves a C(sp²)-CN bond cleavage and tolerates a wide range of functional groups to provide the corresponding aryl nitriles in good yields.
C. Qi, X. Hu, H. He, Synlett, 2016, 27, 1979-1982.

A ZnO-supported palladium(0) nanoparticle catalyst has been applied for the efficient cyanation of a variety of functionalized aryl bromides and activated aryl chlorides with K4[Fe(CN)6] as benign cyanide source. This process circumvents the need for an additive and a ligand and offers high product yields, low catalyst loading (0.2 mol-% Pd), and recyclability of the catalyst.
T. Chatterjee, R. Dey, B. C. Ranu, J. Org. Chem., 2014, 79, 5875-5875.

A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C can be applied to various aryl bromide and active aryl chloride substrates to effect efficient conversions. The process features many advantages over existing cyanation conditions and the practical utility of the process has been demonstrated on scale.
H. Yu, R. N. Richey, W. D. Miller, J. Xu, S. A. May, J. Org. Chem., 2011, 76, 665-668.

A palladium-catalyzed cyanation allows the conversion of highly challenging electron-rich aryl chlorides, in addition to electron-neutral and electron-deficient substrates, as well as nitrogen- and sulfur-containing heteroaryl chlorides under relatively mild conditions in the presence of sterically demanding, electron-rich phosphines as ligands.
A. Littke, M. Soumeillant, R. F. Kaltenbach III, R. J. Cherney, C. M. Tarby, S. Kiau, Org. Lett., 2007, 9, 1711-1714.

An efficient, mild, and inexpensive copper-catalyzed domino halogen exchange-cyanation procedure for aryl bromides was developed. The new method represents a significant improvement over the traditional Rosenmund-von Braun reaction: the use of catalytic amounts of copper and an apolar solvent greatly simplifies the isolation and purification. In addition, the new method exhibits excellent functional group compatibility.
J. Zanon, A. Klapars, S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 2890-2891.

Cyanation of aryl chlorides with potassium hexacyanoferrate(II) catalyzed by a cyclopalladated ferrocenylimine tricyclohexylphosphine complex is applicable to both activated and deactivated aryl chlorides. The corresponding aryl nitriles were isolated in good yields.
Y.-n. Cheng, Z. Duan, T. Li, Y. Wu, Synlett, 2007, 543-546.

Aryl pentafluorobenzenesulfonates and nonaflates were identified to be good substrates for palladium-catalyzed cyanation reactions under very mild conditions using nontoxic, environmentally benign potassium hexacyanoferrate as a cyanide source. A wide range of electronically biased and sterically challenging substrates provided the corresponding the nitriles in very good yields.
M. A. Rajendra, K. Sunil, A. M. Sajith, M. N. Joy, V. A. Bakulev, K. R. Haridas, Synlett, 2020, 31, 1629-1633.

An efficient nickel(II)-catalyzed cyanation of aryl sulfonates, fluorosulfonates, and sulfamates with Zn(CN)₂ provides nitrile products in very good yields in the presence of DMAP as the additive. The method offers wide functional group compatibility.
Y. Gan, G. Wang, X. Xie, Y. Liu, J. Org. Chem., 2018, 83, 14036-14048.

Practical and mild electrochemical cyanations and cyanomethylations of trimethylammonium salts with tosyl cyanide or azido allyl alcohol as the cyanation or cyanomethylation reagents offer high functional group compatibility and can be applied for the cyanation of natural product derivatives. The method avoids the use of an external stoichiometric reducing agent or a sacrificial anode.
X. Kong, Y. Wang, Y. Chen, X. Chen, L. Lin, Z.-Y. Cao, Org. Chem. Front., 2022, 9, 1288-1294.

A Pd/(Me₃Si)₂ system catalyzes a cyanation of commercially available aryldiazonium tetrafluoroborate derivatives with 2-(piperidin-1-yl)acetonitrile under mild conditions to give the corresponding nitrile-containing products in good yields.
M. S. Ahmad, Z. Shafiq, K. Meguellati, Synthesis, 2022, 54, 3077-3084.

The combination of KOAc as base and dcype (1,2-bis(dicyclohexylphosphino)ethane) as ligand is essential for achieving a nickel-catalyzed cyanation of aryl thioethers efficiently. The reaction offers scalability, low catalyst and reagents loadings, and high functional group tolerance.
T. Delcaillau, A. Woenckhaus-Alvare, B. Morandi, Org. Lett., 2021, 23, 7018-7022.

The combination of nickel/dcype is essential to achieve a fully reversible functional group metathesis between aryl nitriles and aryl thioethers in very good yields. This cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules.
T. Delcaillau, P. Boehm, B. Morandi, J. Am. Chem. Soc., 2021, 143, 3628-3637.

A nickel-based catalytic system consisting of a unique diphosphine ligand such as dcype or dcypt enables the cyanation of versatile phenol derivatives such as aryl carbamates and aryl pivalates with aminoacetonitriles as metal-free cyanating agents This method is environmentally benign and easy-to-use.
R. Takise, K. Itami, J. Yamaguchi, Org. Lett., 2016, 18, 4428-4431.

In an efficient nickel-catalyzed deoxycyanation of activated phenolic compounds, relatively nontoxic Zn(CN)₂ can be used as the cyanide source to provide aromatic nitriles in good to excellent yields.
M. M. Heravi, F. Panahi, N. Iranpoor, Org. Lett., 2018, 20, 2753-2756.

Palladium catalysis achieves a direct decarbonylative cyanation of benzoic acids with TMSCN. A wide range of nitriles including those with functional groups was synthesized in good yields. Moreover, this reaction allows late-stage modifications of bioactive molecules such as adapalene, probenecid, telmisartan, and 3-methylflavone-8-carboxylic acid.
T. Xu, W. Li, K. Zhang, Y. Han, L. Liu, T. Huang, C. Li, Z. Tang, T. Chen, J. Org. Chem., 2022, 87, 11871-11879.

A palladium-catalyzed decarbonylative cyanation of inexpensive and stable aryl carboxylic acids provides aryl nitrile compounds. This method enables decarbonylative cyanation of drug molecules and gram-scale reactions.
G. Zhang, H. Miao, C. Guan, C. Ding, J. Org. Chem., 2022, 87, 12791-12798.

A Ni-catalyzed decarbonylative cyanation of acyl chlorides with trimethylsilyl cyanide is applicable to the synthesis of an array of nitrile compounds bearing a wide range of functional groups under neutral conditions.
Z. Wang, X. Wang, Y. Ura, Y. Nishihara, Org. Lett., 2019, 21, 6690-6694.