Isonitrile reactions

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

The isonitrile reaction (p. 167) should be carried out with this salt, and its behaviour on warming with a little nitrite in faintly acid aqueous solution should be examined. 

Isonitrile Reaction.—Like the primary aliphatic amines of the methylamine type, aniline and its analogues give a characteristic odour with chloroform and alkali. 

Staudinger and Kupfer2 discovered a very interesting method for the preparation of diazomethane. They observed that when the isonitrile reaction of primary amines was applied to hydrazine, diazomethane,3 and not the expected di-isocyanogen, C=N—N=C, was produced in the manner indicated in the following equations ... 

With excess HFA a dioxolaneimine 99a is formed from a typical isonitrile reaction mentioned in previous sections. Acidification yields the unsubstituted five-membered ring 99, which is the parent compound of alkylated dioxolanes 99b-e available from isonitriles (R = Me, Et, t-Bu, c-CgHu) 111, 188). Whether the imine structure 99 or the ketone structure 101 has to be assigned to the hydrolysis product is not known. The Chapman rearrangement has been proved in the following system [Eq. (86)] 190). Treatment of 98 with strong bases like l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) yields a spirocyclic compound 100 with elimination of HCN the structure of 100 has been derived by spectroscopic methods 193). The reaction of 98 with HFA X HjO (91) in sulfuric acid produces a l,3-dioxolan-(4)one 112). 

Hofmann s Isonitrile Reaction.—If, however, instead of ammonia we use alkyl primary amines we obtain not the alkyl cyanides but the alkvl iso-cyanides (Cl... 

Isonitriles can otherwise attain tetravalent respectability by participating in cyclization reactions, - and in multicomponent condensations such as the Passerini (3-component) and Ugi (4-component) re-actions. Nitrilium-type intermediates are implicated in many of Aese processes. These isonitrile reactions of major synthetic importance are discussed in detail elsewhere in this compendium. 

While the two colour reactions with bleaching powder and chromic acid are used especially for the recognition of aniline, the isonitrile reaction will show the presence of any primary amine of the aliphatic or aromatic series. The reaction takes place in accordance with the following equation ... 

Lactams from isonitriles Reaction in 2-phase medium... 

Hydrazines substituted only on one nitrogen atom with an aliphatic alkyl give a strong isonitrile reaction. 

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