Electrophilic cyanations

Alkyl or aryl aminothiatriazoles (330) in contrast react with cyanates even at — 70°C to give 5-amidino substituted 1,2,4-thiadiazoles (331) weaker electrophiles, such as isothiocyanates, thiocyanates, and cyanamide do not react with aminothiatriazoles <85JOCl295>. 

It has been demonstrated in CHEC-II <1996GHEC-II(7)431> that halogen substituents as well as other good leaving substituents can be readily replaced by carbon nucleophiles, for example, cyanide ion or active methylene compounds. Also, direct cyanation of l-phenylpyrazolo[3,4-i/]pyrimidine was demonstrated. Since then, reactivity toward carbon nucleophiles has not received much attention. However, a few interesting reactions with carbon electrophiles have been reported in the last few years. Thus, reacting 154 with 155 affords 156 (Equation 9) <2002BML1687>. 

SCHEME 83. Pd-catalyzed cyanation of aryl electrophiles with Zn(CN)2... 

Other examples of electrophilic toxic chemicals are aldehydes and ketones, especially unsaturated ones, acyl halides and cyanates. 

Cyanation of aromatics.1 Viehe s salt (1) effects electrophilic cyanation of aromatic or heteroaromatic systems. 

In this equation, E normally corresponds to hydrogen but can also be another group, e.g. -OCH3. The denotation E is used to show the interplay between nucleophiles and electrophiles in electroorganic reactions. Thus, due to the oxidative nature of the process, a nucleophile can be used as a reagent in an otherwise impossible substitution reaction. As an example of an anodic substitution process, electrochemical cyanation of an aromatic hydrocarbon can be mentioned ... 

Indole, like benzothiophene, reacts with electrophiles to give preferentially -substituted products. Bromination241-243 in dioxane or pyridine, nitration by ethyl nitrate,244 chlorination by sulfuryl chloride,245 iodination in aqueous solution,246, 247 Vilsmeier and Reimer-Tiemann formylations,248-261 diazo coupling,252 thio-cyanation,263 and nitrosation254 all give the 3-substituted indoles, practically free from other isomers. 

Anodic cyanation has been shown to be a direct process by electrochemical methods in conjunction with the analysis of products from cpe experiments (nos. 11 and 34, Table 8). In addition, cyano radicals can be generated in homogeneous solution, and a comparison of processes initiated by radical cation and cyano radical initiated processes reveals the indiscriminate nature of the latter towards aromatic substrates (cf. also Williams, 1960). This is in contrast to the electrophilic nature of the radical cation process. 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

Within the year a wide range of photoreactions in which an aromatic residue undergoes change in substitution has been published. As previously, the diversity of the various processes makes any classification of the reactions unrealistic, and so their order of presentation here is somewhat arbitrary. Aromatic photosubstitution reactions have been reviewed by Parkanyi although the treatment is not extensive, the processes of free radical, electrophilic, and nucleophilic photoinduced substitutions of arenes are well covered.Arene photoreactions initiated by electron transfer with electron donors or acceptors are the subject of a review by Pac and Sakurai. The requirements for the efficient photogeneration of the ion radicals are considered and the synthetic utility of the photoreactions, which include reduction, cyanation, and amination, is discussed. 

Electrophilic attack in imidazole is usually most facile at an annular nitrogen, and there are many examples of Af-aUcylation, -protonation, -acylation, cyanation, -arylation and -silylation. A-Nitration is much less common A-oxidation is virtually non-existent. When an annular nitrogen becomes substituted, tautomerism in the molecules is blocked, and mixtures of isomers are usually formed with substituted benzimidazoles and 4(5)-substituled imidazoles. 

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

Fluoride-induced desilylation-cyanation studies have been undertaken 138) with several electrophilic cyanogen type reagents. The best results were attained 138) when the 1-silyl-l-vinylcyclopropane shown in Scheme 65 was heated in a THF solution containing 4 equivalents of phenylcyanate. This reaction has been used 138> as a key step for the synthesis of ( )-hinesol and of (+)-P-vetivone (Scheme 65). 

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