Cyanating reagents

Optically active cyanohydrins are obtained in good selectivity by the nucleophilic attack of cyanating reagents to chiral acetals.(21) However, the chiral auxiliaries are destroyed, and not recovered. In catalytic processes with chiral boryl compounds,(22) D-oxynitrilase,(23) and synthetic peptides,(24) the optical purities of the resulting cyanohydrins are generally not sufficient. 

Cyanobenziodoxoles 36-38 are used as efficient cyanating reagents toward N,N-dialkylarylamines. In a typical example, reagent 38 reacts with N,N-dimethylanilines 39 in 1,2-dichloroethane at reflux to afford the respective N-cyanomethyl-N-methylanilines 40 in good yield (Scheme 17) [34]. 

The excess of copper cyanide and the use of a polar, high-boiling point solvent makes the purification of the products difficult. In addition, elevated temperatures (up to 200°C) lower the functional group tolerance. The use of alkali metal cyanides or cyanation reagents such as cyanohydrins, a catalytic amount of copper(I) iodide and kalium iodide, allows a mild, catalytic cyanation of various aryl bromides. 

The problem of the hydrocyanation of conjugated carbonyl compounds has been reviewed in detail by Nagata and Yoshioka [281. The reactions proceed smootltly and base or acid catalysts are sometime useful with HCN. Cyanides (KCN. NaCN. etc.) arc recommended reagents in some cases, particularly in nonaqueous Solvents (28], and even cyanohydrins (e.g., acetone cyanohydrin) have been used as cyanation reagents. 

From orthoesters, ketene 0,0-acetals and cyanating reagents 564... 

Most diazonium ions are based on alkyl or aryl groups, but the reactions of aminodiazonium ions and cyanodiazonium ions with aromatic species make them valuable aminating and cyanating reagents. 

The chemical reactivity of cyanobenziodoxoles 133-135 is generally similar to that of azidobenziodoxoles and they can be used as efficient cyanating reagents toward organic substrates [258,296]. 

The use of phosphorus-based cyanation reagents has featured prominently in the recent literature. In particular diethyl phos-phorocyanidate has found varied applications. When used in conjunction with triethylamine conversion of two imidazole-4-... 

In contrast to all the C-C bond formations described previously, C-H cyanations are much rarer. This might be due to the possible strong coordination of free CN ligands to transition metal centers, which would preclude C-H activation as the first step of the catalytic cycle for C-H functionalization. The first C-CN bond formation was reported in 2006 by Yu and coworkers along with a series of Cu-catalyzed and Cu-mediated C-H functionalizations of 2-phenyl pyridine (Scheme 23.24) [88]. C-CN bond formations can thus be achieved with Me SiCN or CH NO as cyanating reagents in the presence of 1 equivalent of Cu(OAc)2 and air. 

Rh-catalyzed direct C-H cyanation of aryl oximes with the cyano transfer group JV-cyano-A/ -phenyl-/)-toluenesulfonamide has tilso been reported [84]. This was the first report of a Rh-catalyzed-directed C-H cyanation reaction for the synthesis of aromatic nitriles. JV-Cyano-JV-phenyl-/)-toluenesulfonamide, a user-friendly cyanation reagent, was used in the transformation. Many different directing groups can be used in this C-H cyanation process, and the reaction tolerates a variety of synthetically important functional groups. This methodology was nicely used for the synthesis of the cyanated derivative of the nonsteroidal anti-inflammatory drug zaltoprofen in a yield of 74% (Scheme 4.12). 

Due to the high price of trimethylsilyl cyanide, access to alternative cyanation reagents is desirable. In this regard, cyanoformate esters (CNCO2R) have been employed, providing direct access to O-alkojycarbonyl-functionalised cyanohydrins, which are stable and not easily hydrolysed by moisture in air. Moreover, they are useful synthetic intermediates and can be applied in the synthesis of a-amino alcohols and (3-substituted unsaturated nitriles from O-carbonylated allylic cyanohydrins. ... 

The efficient trapping of kinetic ketone-enolates with cyanation reagents has previously eluded the synthetic organic chemist. A new procedure has now been developed and utilizes p-toluenesulphonyl cyanide as the cyanation reagent for the preparation of /3-ketonitriles from cyclic ketones (Scheme 27). 

Naked cyanide-acetone cyanohydrin a simple, efficient and stereoselective hydro-cyanating reagent. C. L. Liotta, A. M. Dabdoub and L. H. Zalkow, Tetrahedron Let., 1117(1977)... 

Preparation of Af-Cyano-4-Methyl-A -Phenyl-Benzene-sulfonamide (1). Dehydrative tosylation of iV-phenylurea 2 with p-toluenesulfonyl chloride in pyridine at room temperature gave iV-cyano-4-methyl-iY-phenyl-benzenesulfonamide in 76% yield (eq 1). Notably, title compound 1 is synthesized in a user-friendly and environmentally benign fashion, eliminating the use of toxic cyanation reagents such as BrCN and HCN. Alternative methods of preparation involve the direct tosylation of phenyl cyanamide in pyridine. Structural analogs, such as ben-zenesulfonyl IV-phenyl cyanamide 3 and p-nitrobenzenesulfonyl //-phenyl cyanamide 4, are accessible in a similar manner. ... 

---