Preparation of isocyanides

Scheme 20 Preparation of isocyanides using PS-oxazaphospholidine and their subsequent use in Ugi reaction to give substituted isoindolinones...

The reaction can also be used synthetically for the preparation of isocyanides, though yields are generally not high. An improved procedure has been reported. When secondary amines are involved, the adduct cannot lose 2 mol of HCl. Instead it is hydrolyzed to an iV,A -disubstituted formamide ... 

The cyanide ion is an ambident nucleophile and isocyanides may be side products. If the preparation of isocyanides is desired, they can be made the main products by the use of silver or copper(I) cyanide (p. 459). Vinylic bromides can be converted to vinylic cyanides with CuCN, with KCN, a crown ether, and a... 

A less conventional preparation of isocyanide complexes involves the reaction of iron pentacarbonyl with metalated (sodium or lithium derivative) hexamethyldisilazane (162). 

A general procedure has been outlined for the preparation of isocyanide complexes of Wn (equations 23, 24).316 [W(CNR)7]2+ (R = CMe3, C6HU) can also be prepared by reaction of the... 

Among the features of Volume 41 is the smallest-scale synthesis yet published in Organic Syntheses, namely, the preparation of 0.0005 mole of cholestanyl methyl ether by a generally useful methylation procedure that employs diazomethane and fluoboric acid (p. 9). Two preparations of isocyanides by dehydration of formamides are included. One of these, illustrated by cyclohexyl isocyanide (p. 13), is most suitable for aliphatic isocyanides while the other, illustrated by o-tolyl isocyanide (p. 101), is most suitable for aromatic isocyanides. 

An interesting and novel method for the preparation of isocyanides (85) has been reported and represents a new method for the preparation of these compounds in excellent yields. Thus with a variety of alkyl and aryl carbonimidoyl dichlorides (84) cathodic reduction in the range -1.25 V to -1.90 V (see) provides a new, mild and reagent-free method for the preparation of isocyanides in 82-96% yields, as determined by gas chromatography (equation 49)71. 

In addition to its use in the preparation of nitriles, trimethylsilyl cyanide (TMS-CN) is also becoming a very useful reagent for the preparation of isocyanides. 1-Chloroadamantane, for instance, gives rise to 78% of the corresponding isonitrile in the presence of catalytic amounts of TiCU (Scheme 26). Of special interest is the remarkably regioselective and stereoselective synthesis of trimethylsilyloxyalkyl isocyanides (Scheme 26) from oxiranes and TMS-CN in the presence of, for example, zinc halides (see also Section 1.8.1.3). < ... 

Isocyanides,4 In the previously preferred method of preparation of isocyanides, a formamide is dehydrated by the combination of phosphoryl chloride with either pyridine or potassium t-butoxide (1, 878). In a recently reported procedure the ternary... 

Preparation of isocyanides. Ugi, in an Organic Syntheses procedure, used POCla in pyridine to dehydrate N-cyclohexylformamide to cyclohexyl isocyanide, but in a later paper he expressed preference for phosgene (see Phosgene). The procedure preferred for aryl isocyanides is illustrated for o-tolyl isocyanide. A suspension of potassium t-butoxide in t-butanol is prepared under nitrogen, N-o-... 

Preparation of isocyanides. A general method for the preparation of aryl isocyanides (Ugi ) is exemplified by the preparation of o-tolyl isocyanide. A suspension of potassium /-butoxide in /-butanol is prepared under nitrogen by stirring a mixture... 

The realization that this was a new type of compound, isomeric to the nitriles, and the elaboration of the classical methods for the preparation of isocyanides, the alkylation method and the carbylamine method by Gautier and Hofmann, initiated an active period of isocyanide chemistry that ended by the turn of the century with Nef s investigations on the reactions of the formally divalent carbon atom in the isocyanides. - TTie discovery of the Passerini reaction in 1921 led to a brief renaissance of isocyanide chemistry. 

Since then most isocyanides have become readily available by the transformation (1) -> (2), the method of choice for the preparation of isocyanides. The best dehydrating agents for (1) are phosgene and diphosgene in the presence of triethylamine, and phosphorus oxychloride in the presence of diiso-propylamine. °... 

Displacement of ligating dinitrogen by isocyanides constitutes a convenient route for the preparation of isocyanide complexes. The first isocyanide complexes prepared by this route involve a molybdenum(0) or tungsten(0) electron-rich metal site, and the general method for their synthesis is given below. 

Molins E, Labarta A, Tejada J, Caubet A, Alvarez S (1983) Transition Met Chem 8 377 For preparation of isocyanides see ... 

Reactions of metal cyanides with various compounds leading to the preparation of isocyanide complexes have less significance at present, because synthetic methods that utilize isocyanides as substrates have been developed. Nevertheless, metal cyanides are still used in the case of synthesis of complexes with unstable or unattainable isocyanides... 

At present, this method is often used for the preparation of isocyanide complexes. During reaction, the addition of the ligand may take place without the change of the oxidation state. However, in many cases, reduction of the metal occurs, and complexes in which the transition element has a lower oxidation state than the starting compound are obtained. Copper (I) salts coordinate one to four RNC molecules to give [CuX(CNR) ] and [Cu(CNR)4]X. Copper(II) salts are readily reduced by isocyanides to Cu(I) compounds. However, copper(II) chlorate or tetrafluoroborate and tert-dikyl isocyanide give the cationic complex [Cu(CNR)4]X2. This compound must immediately be separated from the reaction mixture in order to avoid its reduction. 

Di-2-pyridyl sulfite 1660 is presented as a useful reagent for the preparation of isocyanides under mild conditions [1230], Yields given in the table therein are good (70-82% for test alkyl, benzylic, and aryl isocyanides). The reagent (prepared from 2-hydroxypyridine 1659 and thionyl chloride) is rather unstable, but can be stored in a refrigerator for a week without decomposition , according to the authors. 

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