Oxovanadium(V)-catalyzed enantioselective Meerwein-Ponndorf-Verley cyanation of aldehydes using acetone cyanohydrin

Oxovanadium(V)(salen) complex 4 was found to catalyze Meerwein-Ponndorf-Verley cyanation of aliphatic aldehydes with good to high enantioselectivity. This cyanation showed a positive nonlinear effect.     

Copper-Mediated Selective Cyanation of Indoles and 2-Phenylpyridines with Ammonium Iodide and DMF

Copper-mediated regioselective cyanation of indoles and 2-phenylpyridines was developed by using ammonium iodide and DMF as the combined source of a cyano unit under "Pd-free" conditions. Mechanistic studies indicate that the reaction of indoles proceeds through a two-step sequence: electrophilic initial iodination and then cyanation. The cyanation has a broad substrate scope, high functional group tolerance, and excellent regioselectivity.     

Palladium-assisted regioselective C-h cyanation of heteroarenes using isonitrile as cyanide source

A palladium-catalyzed regioselective C-H cyanation of heteroarenes was achieved using tert-butyl isocyanide as "CN" source, which provides a new and unique strategy for the preparation of (hetero)aryl nitriles. Indoles, pyrroles, and aromatic rings could be efficiently cyanated through C-H bond activation with high regioselectivity.     

Progress in the palladium-catalyzed cyanation of aryl chlorides

The development of new palladium catalysts for the cyanation of various aryl and heteroaryl chlorides is described. The combination of amine co-catalysts with chelating phosphine ligands, for example, 1,4-bis(diphenylphosphino)butane (dppb) or 1,5-bis(diphenylphosphino)pentane (dpppe), allows an efficient cyanation of chloroarenes with simple potassium cyanide. General palladium-catalyzed cyanation of nonactivated and deactivated chloroarenes is possible for the first time. Studies of the oxidative addition of aryl halides to palladium triphenylphosphine complexes in the presence and absence of amines suggest that the co-catalyst is capable of preventing catalyst deactivation caused by the presence of excess cyanide ions in solution.     

Ester-functionalized phthalonitriles and zinc phthalocyanines via palladium-catalyzed cyanation of 4,5-dichlorophthalates

Dicyanophthalates 3 were synthesized via Pd-catalyzed two-fold cyanation of the corresponding 4,5-dichlorophthalates with Zn(CN)₂. Appropriate modification of reaction conditions allowed one-pot synthesis of the corresponding zinc phthalocyanines 7 bearing eight peripheral alkyl ester groups. Powder X-ray diffraction study of a mesogenic zinc phthalocyanine bearing branched alkyl substituents revealed a rare case of a transition between two columnar rectangular liquid crystalline mesophases with different symmetry.     

DMAP-catalyzed cyanation of aldehydes and ketones with ethyl cyanoformate

The cyanation of carbonyl compounds with ethyl cyanoformate is catalyzed by 4-dimethylaminopyridine (DMAP) to afford the corresponding cyanohydrin carbonates in excellent yields. The system provides a convenient method for cyanation of carbonyl compounds without using metal catalysts or solvents.     

Highly enantioselective cyanation of aldehydes catalyzed by a multicomponent titanium complex

A new multicomponent bifunctional catalytic system based on a titanium complex was used for the efficient enantioselective cyanation of aldehydes. The catalyst was readily prepared from tetraisopropyl titanate (Ti(Oi-Pr)4), (S)-6,6'-dibromo-1,1'-bi-2-naphthol (1e), cinchonine (2a), and (1R,2S)-(-)-N-methylephedrine (3b). It was revealed that the combination of 1e, 2a, 3b, and Ti(IV) was essential in this cyanation. The reaction proceeded smoothly in the presence of a catalytic amount of the multicomponent catalyst to afford the desired cyanohydrins ethyl carbonates in moderate to excellent isolated yields (up to 95%) with high enantioselectivities (up to 94% ee). A catalytic cycle based on experimental phenomena was proposed to explain the origin of the asymmetric induction.     

Studies on pyrazines. 16 . Palladium-catalyzed cyanation of 2-amino-5-bromopyrazines

We report here a synthesis of 2-amino-5-cyano- 3 and 2-amino-3,5-dicyanopyrazines 4 by palladium(0)-catalyzed cyanation of the corresponding pyrazine amino bromides 1 and 2.     

Mild and efficient copper-catalyzed cyanation of aryl iodides and bromides

An efficient copper-catalyzed cyanation of aryl iodides and bromides is reported. Our system combines catalytic amounts of both copper salts and chelating ligands. The latter, which have potential nitrogen- and/or oxygen-binding sites, have never previously been used in this type of reaction. A protocol has been developed that enables the cyanation of aryl bromides through the copper-catalyzed in situ production of the corresponding aryl iodides using catalytic amounts of potassium iodide. Aryl nitriles are obtained in good yields and excellent selectivities in relatively mild conditions (110 degrees C) compared with the Rosenmund-von Braun cyanation reaction. Furthermore, the reaction is compatible with a wide range of functional groups including nitro and amino substituents. The protocol reported herein involves two main innovations: the use of catalytic amounts of ligands and the use of acetone cyanohydrin as the cyanating agent in copper-mediated cyanation reactions.     

The di-iron subsite of all-iron hydrogenase: mechanism of cyanation of a synthetic [2Fe3S]-carbonyl assembly

This paper describes the kinetics and intimate mechanisms associated with cyanation of [2Fe3S] assemblies to give species structurally related to the subsite of all-iron hydrogenase. Stopped-flow FTIR spectroscopy has enabled the quantitation of the dynamics of five well-defined steps that experimentally illustrate the role of bridging carbonyls in the assembly of the dicyanide species, how on-off sulfur ligation can have a dramatic effect on cyanation kinetics and how the [2Fe3S] core stabilises bridging carbonyl species.     

Vanadium-catalyzed oxidative Strecker reaction: α-C–H cyanation of para-methoxyphenyl (PMP)-protected primary amines

We describe an oxidative Strecker reaction that allows for direct cyanation of para-methoxyphenyl (PMP)-protected primary amines. A vanadium(V) complex was used as the catalyst and TBHP as the oxidant. The cyanation occurs at the α-C position bearing either an alkyl or an aromatic group. This method provides a direct access to α-aminonitrile from amines with one-carbon extension.     

阳极氰化反应的研究进展

本文综述了近30年来阳极氰化反应在有机电合成中的应用,主要回顾了阳极氰化胺、阳极氰化杂环化合物和阳极氰化芳香化合物的研究.此外,还报道了乳化技术在阳极氰化反应中的应用.     

Synthesis of symmetrical amino and aminomethyl derivatives of Tröger's base via Pd-catalyzed C-C and C-N bond formation

In this paper, we report the synthesis of amino and aminomethyl derivatives of Tröger's base (±)-1 and (±)-2. The key steps in the synthesis of (±)-1 and (±)-2 are Pd-catalyzed amination and cyanation, respectively, of the easily accessible dihalo derivatives (±)-3. These compounds are important intermediates in the synthesis of new ligands and building blocks for H-bonded supramolecular architectures.     

Facile Synthesis of 3‐Hydroxyglutamic Acids via Cyanation of Chiral N‐Acyliminium Cation Derived From (S)‐Malic Acid

Facile synthesis of 3‐hydroxyglutamic acids via cyanation of an N‐acyliminium intermediate derived from (S)‐malic acid is described. The chiral cyclic imide derived from (S)‐malic acid was converted to an acetoxylactam by reduction with sodium borohydride followed by acetylation. The obtained acetoxylactam was treated with trimethylsilyl cyanide in the presence of boron trifluoride etherate to give the corresponding cyanolactam in high yield, even though the diastereoselectivity of the cyanation reaction was moderate. The diastereomers of the cyanolactam were chromatographically separable and were independently converted to (2R,3S)‐ and (2S,3S)‐3‐hydroxyglutamic acids.     

Transition‐Metal‐Catalyzed Cyanation by Using an Electrophilic Cyanating Agent,N‐Cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS)

The ability to introduce a nitrile group into a biologically active compound is very useful in organic synthesis, owing to the importance of nitrile groups in transformations and tuning molecular properties. To date, nucleophilic cyanation has been the most used strategy for this purpose, whilst electrophilic cyanation reactions are less developed. Recently, the electrophilic cyanation reagent N‐cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) has received increasing attention, owing to its superior properties in terms of safety and practicality. This Focus Review summarizes recent progress in transition‐metal‐catalyzed cyanation reactions that use NCTS.     

C(sp3)–H cyanation by a formal copper(iii) cyanide complex

High-valent metal oxo complexes are prototypical intermediates for the activation and hydroxylation of alkyl C–H bonds. Substituting the oxo ligand with other functional groups offers the opportunity for additional C–H functionalization beyond C–O bond formation. However, few species aside from metal oxo complexes have been reported to both activate and functionalize alkyl C–H bonds. We herein report the first example of an isolated copper(iii) cyanide complex (LCu^IIICN) and its C–H cyanation reactivity. We found that the redox potential (E_ox) of substrates, instead of C–H bond dissociation energy, is a key determinant of the rate of PCET, suggesting an oxidative asynchronous CPET or ETPT mechanism. Among substrates with the same BDEs, those with low redox potentials transfer H atoms up to a million-fold faster. Capitalizing on this mechanistic insight, we found that LCu^IIICN is highly selective for cyanation of amines, which is predisposed to oxidative asynchronous or stepwise transfer of H⁺/e⁻. Our study demonstrates that the asynchronous effect of PCET is an appealing tool for controlling the selectivity of C–H functionalization.

A formal copper(iii) cyanide complex and its C–H cyanation reactivity are reported. The redox potentials of substrates, instead of C–H bond dissociation energies, were found to be the key determinant of the rates of PCET.     

Lewis acid catalyzed direct cyanation of indoles and pyrroles with N-cyano-N-phenyl-p-toluenesulfonamide (NCTS)

BF(3)·OEt(2)-catalyzed direct cyanation of indoles and pyrroles using a less toxic, bench-stable, and easily handled electrophilic cyanating agent N-cyano-N-phenyl-para-toluenesulfonamide (NCTS) affords 3-cyanoindoles and 2-cyanopyrroles in good yields with excellent regioselectivity. The substrate scope is broad with respect to indoles and pyrroles.     

Cyanide-Free Cyanation of sp2 and sp-Carbon Atoms by an Oxazole-Based Masked CN Source Using Flow Microreactors

This work reports a cyanide-free continuous-flow process for cyanation of sp² and sp carbons to synthesize aryl, vinyl and acetylenic nitriles from (5-methyl-2-phenyloxazol-4-yl) boronic acid [OxBA] reagent as a sole source of carbon-bound masked −CN source. Non-toxic and stable OxBA reagent is generated by lithiation-borylation of bromo-oxazole, and the consecutive Suzuki-Miyaura cross-coupling with aryl, vinyl, or acetylenic halides and demasking [4+2]/retro-[4+2] sequence were successfully accomplished to give the desired cyano compounds with reasonably good yields in a four-step flow manner. A unique feature of this cyanation protocol in flow enables to cyanate a variety of sp² and sp carbons to produce a broad spectrum of aryl acetonitrile. It is envisaged that the OxBA based cyanation would replace existing unstable and toxic approaches as well as non-toxic cyanation using two different sources of “C” and “N” to incorporate the −CN group.     

Shape-dependent catalytic activity of copper oxide-supported Pd(0) nanoparticles for Suzuki and cyanation reactions

Palladium nanoparticles supported on different shapes of nanocrystalline CuO are prepared by the treatment of Cu(NO₃)₂ and Pd(OAc)₂ in polyethylene glycol (PEG-6000). The shapes of the CuO/Pd composite are dependent on the amount of PEG used. Suzuki coupling was catalyzed efficiently by the oval-shaped material, whereas the rod shape facilitates the cyanation reaction. The CuO/Pd catalyst is recovered and reused for subsequent Suzuki reactions; however, cyanation poisons the catalyst for further use. Both these reactions are very clean and high yielding.     

Visible-light-induced cyanation of aza-Baylis–Hillman adducts: a Michael type addition

Visible-light-induced aerobic oxidative cyanation of aza-Baylis–Hillman (aza-BH) adducts providing valuable allylic cyanides in good to excellent yields has been developed. The protocol involves in situ formation of 4π conjugated iminium ion intermediates, which undergo cyanation at the γ-position to afford Michael type adducts. This is the first example of visible-light-induced catalytic functionalization of aza-BH adducts using air (O₂) as an economical and ecosustainable oxidant and TMSCN as a convenient and readily available cyanide source.