Cyanations Grignard reagents

A cyanobenzo[6]thiophene may be converted into the corresponding amidino compound by successive treatment with ammonium cyanate and acid.561 2- -Cyanophenylbenzo[6]thiophene has been used to prepare the corresponding isocyanato compound, but no details have been given.302 The hydrolysis of cyanobenzo[6]thiophenes is discussed in Section VI, M, 2 their reaction with Grignard reagents is discussed in Section VI, L, 3, a. 

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. ... 

The preparation of alkyl, alkenyl, and aryl derivatives of cyanoacetylene (1) poses no particular problems. In most cases a terminal acetylene is metalated or converted into an alkynyl Grignard reagent, and these intermediates are subsequently intercepted by a cyano source , which in most cases is either cyanogen chloride or bromide and sometimes cuprous cyanide or phenyl cyanate. Of course, dehydration of an acetylenic amide as described for the parent molecules is also possible and has occasionally been employed. 

From the Grignard reagent (prepared from the alkyl halide and magnesium in dry ether) with phenyliso-cyanate in ether... 

Apart from the already mentioned Pd-catalyzed coupling reactions it can be predicted that other coupling reactions will be of value to industry in the foreseeable future. Among others, coupling reactions of aryl hahdes with Grignard reagents, antinations, cyanations. 

A method for the electrophilic cyanation of aryl- and heteroaryl-bromides has been developed using A-cyano-(V-phenyl-p-toluenesulfonamide as the cyanide source. The procedure involves generation of Grignard reagents from the aryl bromides prior to... 

In addition, derivatives are described whose preparation is based on the preparation of a Grignard reagent. This reagent, when reacting with cyanates, affords solid derivatives suitable for identification. The procedure can be expressed by the following scheme ... 

The reaction has been shown to be of very broad scope with a multitude of nucleophiles Nu such as imides.23,24,29,32,33,36,37,42 amines,10,32 cyanide,25,32 hydroxide,10,32 alkox-ide,10,26,32 electron-rich isocyclic or heterocyclic aromatic compounds,28 carboxamides,31 lactams,31 ureas,31 sulfonamides,31 cyanate,31 formate (to give products with Nu = H),34 C-H acidic compounds,35 hydrazines and hydrazides,38 and sulfinates.38 The amino group NR R2 of cyclopropane-1,1-diamines and the nucleophile Nu in bicycles 8, 9 or 12, respectively, can be easily replaced with other nucleophiles Nu, such as water,10,32,33 alkoxide,10,32-34,42 Grignard compounds,27,42 amines,29,30,36,37,42,43 cyanide,29,33,42,44 hydride,34,42,44 and C-H acidic compounds39-41,43,44 (see Section 5.2.1.). Therefore, it is currently the most important method for the preparation of substituted bicyclic cyclopropylamines. The toxic and costly reagent methyl fluorosulfate can be avoided in a modified synthetic route, which instead of the fluorosulfate 5 proceeds via the corresponding tetraphenylborate, hexafluorophosphate, or (most conveniently) via the tosylate.23 The different steps of the method can often be combined in a one-pot procedure. Results are summarized in Table 3. 

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