Nickel-Catalyzed Cyanation Research Articles

Nickel-Catalyzed Cyanation of Allylic Alcohols: High Degree of Chiral Inversion in Aqueous Reaction Media.

Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion. The accelerated release of cyanide in H2O was crucial for the success of this reaction.

Ni-Catalyzed Reductive Cyanation of Alkenyl Tosylates and Triflates

Herein, we disclose the nickel-catalyzed reductive cyanation of alkenyl tosylates and triflates. Both cyclic and acyclic alkenyl nitriles are produced in moderate to good yield using 2-(4-methoxyphenyl)-2-methylmalononitrile (MeO-MPMN), a novel...

Nickel-Catalyzed Cyanation of (Hetero)aryl Bromides Using DABAL-Me3 as a Soluble Reductant.

A nickel-catalyzed cyanation of (hetero)aryl halides using air-stable bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane (DABAL-Me3) as a soluble reductant has been developed. The reaction uses readily available and inexpensive Ni(dppf)Cl2 as a precatalyst, a substoichiometric amount of Zn(CN)2, and DABAL-Me3 as an alternative to commonly prescribed insoluble reductants. We found the addition of catalytic tetrabutylammonium bromide (TBABr) to be beneficial, due to facilitating dissolution of low levels of the cyanide salt (confirmed via a control study). Similarly, slow addition of a tetrabutylammonium cyanide (TBACN) solution is effective and results in a completely homogeneous reaction mixture.

DFT studies on the mechanisms of nickel-catalyzed reductive-coupling cyanation of aryl bromide

The mechanisms of nickel-catalyzed cyanation of aryl halides with 2-methyl-2-phenylmalononitrile (MPMN) through the reductive-coupling reactions have been investigated using density functional theory (DFT) calculations. The NiI catalytic cycle was more favored over the Ni° catalytic cycle. The results showed that the overall catalytic cycle included the oxidative addition, reduction, 1,2-migratory insertion, β-C elimination, product separation and catalyst regeneration steps. We calculated the high spin state of triplet Ni catalytic cycle and the low spin state of singlet Ni catalytic cycle. The results showed that the rate-determining step in the whole catalytic cycle was the oxidative addition step where the Gibbs free energy barrier ΔGsol in N,N-dimethylacetamide (DMA) solution is 14.8 kcal/mol, which kept consistent with the experimental results.

Air-Tolerant Nickel-Catalyzed Cyanation of (Hetero)aryl Halides Enabled by Polymethylhydrosiloxane, a Green Reductant.

An air-tolerant nickel-catalyzed cyanation of aryl bromides is reported. The reaction uses a NiCl2/Xantphos catalyst in combination with substoichiometric quantities of zinc cyanide and polymethylhydrosiloxane. This silane is a green, homogeneous alternative to the traditional, insoluble solid reductant zinc and renders the reaction tolerant to air. The reaction can be performed under an air atmosphere, obviating the need for degassing, a glovebox, or Schlenk techniques. The reaction scope is broad, proceeding in good yields with a variety of (hetero)arenes.

Nickel-catalyzed cyanation reaction of aryl/alkenyl halides with alkyl isocyanides.

We herein describe a nickel-catalyzed cyanation reaction of aryl/alkenyl halides with alkyl isocyanides. Both aryl/alkenyl iodines and bromides were found to be competent electrophiles that reacted with alkyl isocyanides, affording nitrile compounds in moderate to good yields. A range of functional groups including halogens as well as hydroxyl, formyl, and acetamino groups were fairly compatible with the nickel catalysis. This protocol featured broad functional group tolerance, simple reaction conditions, and gram-scale synthesis.

Nickel-Catalyzed Cyanation of Aryl Thioethers

A nickel-catalyzed cyanation of aryl thioethers using Zn(CN)2 as a cyanide source has been developed to access functionalized aryl nitriles. The ligand dcype (1,2-bis(dicyclohexylphosphino)ethane) in combination with the base KOAc (potassium acetate) is essential for achieving this transformation efficiently. This reaction involves both a C-S bond activation and a C-C bond formation. The scalability, low catalyst and reagents loadings, and high functional group tolerance have enabled both late-stage derivatization and polymer recycling, demonstrating the reaction's utility across organic chemistry.

Nickel-Catalyzed Deaminative Cyanation: Nitriles and One-Carbon Homologation from Alkyl Amines.

A nickel-catalyzed deaminative cyanation of Katritzky pyridinium salts has been developed. When it is coupled with formation of the pyridinium salt from primary amines, this method enables alkyl amines to be converted to alkyl nitriles. A less toxic cyanide reagent, Zn(CN)2, is utilized, and diverse functional groups and heterocycles are tolerated. The method also enables a one-carbon homologation of alkyl amines via reduction of the nitrile products, in addition to many other potential transformations of the versatile nitrile group.

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

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 benig...

Nickel-Catalyzed Cyanation of (Hetero)arenes

Nickel-Catalyzed Cyanation of (Hetero)arenes

New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,2'-Bis(aminomethyl)-1,1'-binaphthyl.

As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C–N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,2′-bis(aminomethyl)-1,1′-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimolar amount of [IrCl2Cp*]2 (Cp* = η5–C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C–H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.

Carbon Dioxide and Ammonia as Cyanide Source in Nickel-Catalyzed Reductive Cyanation of Aryl Chlorides

Key words nickel catalysis - cyanation - carbon dioxide - ammonia

Nickel-Catalyzed Cyanation of Unactivated Alkyl Sulfonates with Zn(CN)2.

Cyanation of unactivated primary and secondary alkyl mesylates with Zn(CN)2 catalyzed by nickel has been developed. The reaction provides an efficient route for the synthesis of alkyl nitriles with wide substrate scope, good functional group tolerance, and compatibility with heterocyclic compounds. Mechanistic studies indicate that alkyl iodide generated in situ serves as the reactive intermediate and the gradual release of alkyl iodide is crucial for the success of the reaction.

Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos\u2013Ni(I) species

Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO2/NH3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.

Nickel-Catalyzed Cyanation of Aryl Halides and Hydrocyanation of Alkynes via C–CN Bond Cleavage and Cyano Transfer

We report nickel-catalyzed cyanation and hydrocyanation methods to prepare aryl nitriles and vinyl nitriles from aryl halides and alkynes, respectively. Using inexpensive and nontoxic 4-cyanopyridi...

Nickel-catalyzed cyanation of aryl halides and triflates using acetonitrile via C-CN bond cleavage assisted by 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine.

We developed a non-toxic cyanation reaction of various aryl halides and triflates in acetonitrile using a catalyst system of [Ni(MeCN)6](BF4)2, 1,10-phenanthroline, and 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine (Si-Me4-DHP). Si-Me4-DHP was found to function as a reductant for generating nickel(0) species and a silylation reagent to achieve the catalytic cyanation via C-CN bond cleavage.

Nickel-Catalyzed Cyanation of Unactivated Alkyl Chlorides or Bromides with Zn(CN)2.

A nickel-catalyzed cyanation of unactivated secondary alkyl chlorides or bromides using less toxic Zn(CN)2 as the cyanide source has been developed. The reaction features the use of air-stable and inexpensive NiCl2·6H2O or Ni(acac)2 as the precatalysts and offers an efficient synthesis of a broad range of alkyl nitriles. Cyanation of primary alkyl chlorides or bromides was also achieved by reaction with Zn(CN)2 in the presence of n-Bu4NCl without the need of nickel catalyst.

Nickel-Catalyzed Cyanation of Phenol Derivatives with Zn(CN)2 Involving C-O Bond Cleavage.

An efficient nickel-catalyzed cyanation of aryl sulfonates, fluorosulfonates, and sulfamates with Zn(CN)2 was developed, which provides a facile access to the nitrile products in generally good to excellent yields. The reaction is accomplished by using NiII complex as the precatalyst and DMAP as the additive. The method also displays wide functional group compatibility; for example, keto, methoxy, N, N-dimethylamino, cyano, ester, and pyridyl groups are well-tolerated during the reaction process.

Nickel-Catalyzed Cyanation of Benzylic and Allylic Pivalate Esters.

A nickel-catalyzed cyanation reaction of benzylic and allylic pivalate esters is reported using an air-stable Ni(II) precatalyst and substoichiometric quantities of Zn(CN)2. Alkene additives were found to inhibit catalysis, suggesting that avoiding β-hydride elimination side reactions is essential for productive catalysis. An enantioenriched allylic ester undergoes enantiospecific cross-coupling to produce an enantioenriched allylic nitrile. This method was applied to an efficient synthesis of (±)-naproxen from commercially available starting materials.

Nickel-catalyzed cyanation of phenol derivatives activated by 2,4,6-trichloro-1,3,5-triazine.

A nickel-catalyzed cyanation of phenol derivatives activated by 2,4,6-trichloro-1,3,5-triazine (TCT) using aminoacetonitrile as the cyanating agent is described. This catalytic system delivered the desired products in moderate to good yields with good substrate compatibility. The readily available starting materials, cost-effective nickel catalyst and metal-free cyanating agent are the major features of the present method.