A mild and efficient palladium-catalyzed cyanation of aryl chlorides with K4[Fe(CN)6

An efficient palladium-catalyzed cyanation of aryl chlorides is established. In the presence of a highly effective Pd/CM-phos catalyst, cyanation of aryl chlorides proceeds at 70 °C in general, which is the mildest reaction temperature achieved so far for this process. Common functional groups such as keto, aldehyde, ester, nitrile and -NH(2), and heterocyclic coupling partners including N-H indoles are well tolerated. Moreover, a sterically hindered nonactivated ortho,ortho-disubstituted electrophile is shown to be a feasible coupling partner in cyanation.     

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.     

Synergistic Heterobimetallic Manifold for Expedient Manganese(I)‐Catalyzed C−H Cyanation

The manganese‐catalyzed cyanation of inert C?H bonds was achieved within a heterobimetallic catalysis regime. The manganese(I) catalysis proved widely applicable and enabled C?H cyanations on indoles, pyrroles and thiophenes by facile C?H manganesation. The robustness of the manganese catalyst set the stage for the racemization‐free C?H cyanation of amino acids with excellent levels of positional and chemo selectivity by the new cyanating agent NCFS. Experimental and computational mechanistic studies provided strong support for a synergistic heterobimetallic activation mode, facilitating the key C?C formation.     

A palladium-catalyzed one-pot procedure for the regioselective dimerization and cyanation of indoles

A one-pot method for the regioselective dimerization and cyanation of indoles has been developed. The reaction uses safe and nontoxic K₄[Fe(CN)₆]·3H₂O as the cyanating agent which introduces selectively a cyano group into the 3-position of biindoles with high efficiency.     

Novel and direct oxidative cyanation reactions of heteroaromatic compounds mediated by a hypervalent iodine(III) reagent

The hypervalent iodine(III) reagent phenyliodine bis(trifluoroacetate) (PIFA) mediates the selective cyanation reactions of a wide range of electron-rich heteroaromatic compounds such as pyrroles, thiophenes, and indoles under mild conditions. These reactions proceed via a cation radical intermediate, and the key for the successful transformation presumably depends on the oxidation-reduction potential of the substrates used. The synthetic utility has been demonstrated through the conversion of these biologically important pyrroles 2f and 2g. [reaction: see text]     

A facile and efficient synthesis of 3‐cyanoindoles by a simple palladium(II)‐catalyzed C─H activation of indoles

An efficient trans ‐PdCl₂(NH₂CH₂COOH)₂‐catalyzed direct C3‐cyanation of indole C─H bonds is described. Notably, free (N─H)‐indoles reacted smoothly using the procedure, and the desired product 3‐cyanoindoles were obtained in good to excellent yields.     

The palladium-catalyzed cyanation of indole C-H bonds with the combination of NH4HCO3 and DMSO as a safe cyanide source

A palladium-catalyzed cyanation of the 3-position of indole sp(2) C-H bonds by the combination of NH(4)HCO(3) and DMSO as the "CN" source was achieved to provide aromatic nitriles in moderate to good yields with excellent regioselectivity. It represents a practical and safe cyanation method.     

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.     

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.     

Transition Metal‐Participated Synthesis and Utilization of N‐containing Heterocycles: Exploring for Nitrogen Sources

This account aims to describe our recent efforts on the synthesis and utilization of N‐containing heterocycles, where transition metals participate in the synthesis. A variety of nitrogen sources, including amines, amides, hydrazones, pyrimidines, isocyanides, and copper nitrate, have been disclosed for the synthesis of diverse bioactive and pharmacologically interesting N‐containing heterocycles under the participation of transition metals. The well‐known nitrogen sources, such as amines and amides, were used for the construction of indoles, isatins, and quinolones. Dihydrophthalazines, isoquinolines, indazoles, and pyrazoles were obtained from hydrazones, while various pyrimidine‐containing heterocycles were afforded through regioselective C?H functionalizations using pyrimidine as the directing group. Recent research has focused on the chemistry of isocyanides to achieve several kinds of heterocyclic compounds with high efficiency under the catalysis of transition metals (Pd, Rh, Mn, Cu), through oxidative cyanation reactions, sequential isocyanide insertions into C?H, N?H, or O?H bonds, and tandem radical annulation. More recently, an efficient route to isoxazolines has been reported using copper nitrate as a novel nitrogen source.     

Optimisation and scale-up of microwave assisted cyanation

A microwave enhanced palladium catalysed cyanation procedure was optimised for the final step of a production method for citalopram 2. The method was demonstrated on multigram batch scale for the synthesis of escitalopram (S)-2 and then in a stop-flow continuous process for citalopram.     

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.     

A facile approach to the synthesis of 5,7-disubstituted indoles via a highly selective lithium-bromine exchange of 5,7-dibromoindoles

A general approach to the synthesis of 5,7-disubstituted indoles has been developed based upon a highly selective lithium-bromine exchange reaction at the 7-position when 1-alkyl-5,7-dibromoindoles were treated with t-BuLi in ether. The resulting 5-bromo-7-lithiated indoles could react with various electrophiles to afford 5-bromo-7-substituted indoles (6) upon work-up. Without isolation of 6, the intermediates thus obtained could be exposed to a second lithium-bromine exchange reaction in a one-pot procedure and further reacted with various electrophiles to afford 5,7-disubstituted indoles (1).     

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.     

Dihydropyrrolo[3,4-b]- and dihydropyrimido[4,5-b]indoles

Aromatic aldehydes react with indole-2-carboxylic acid azides under acid catalysis conditions to give the corresponding 3-(-halobenzyl)indoles, which react with aliphatic and aromatic amines to give the corresponding aminobenzylindoles. The latter undergo intramolecular cyclization to dihydropyrrolo[3,4-b]indoles at room temperature and are converted to dihydropyrimido[4,5-b]indoles through the Curtius rearrangement when they are heated to 80-110°C. Acetylation of the latter products gives N- and O-acetyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 935–939, July, 1982.     

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.     

Reaction of 1-(R-Sulfonyl)indoles with N,N-Dibenzyl-β-amino Alcohols

The reaction of 1-(methylsulfonyl)- and 1-(phenylsulfonyl)indoles with N,N-dibenzylamino alcohols leads to the formation of a mixture of isomeric 1-(-aminoethyl)indoles.     

Stereoselective Palladium‐Catalyzed Carboaminoxylations of Indoles with Arylboronic Acids and TEMPO

Indoles are not indolent : Various indoles react with arylboronic acids chemodivergently. C? H arylation of free indole and N‐methylindole gives the corresponding C(2)‐arylated indoles A whereas N‐acylated, N‐benzoylated, and N‐Boc‐protected indoles provide the corresponding arylcarboaminoxylated products B with excellent diastereoselectivity in good to excellent yields.

     

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.     

[1,2]-Aryl migration in the synthesis of substituted indoles: scope, mechanism, and high throughput experimentation

A mild regioselective synthesis of substituted indoles from readily accessible 1-(2-aminophenyl)-2-chloroethanones is described. Addition of a range of carbon nucleophiles to α-chloro acetophenones 1 generates 2-substituted indoles 2 in moderate to excellent yields. A reaction mechanism involving a [1,2]-aryl migration is proposed. This useful transformation is further examined using high throughput experimentation.