Isocyanides, reaction with nitrones

Reactions of fluoroalkylketenimines which have been reported following these newly available synthetic approaches include hydrolysis and related additions of amines and alcohols, all of which occur at the olefinic bond. In contrast, the apparently similar addition of secondary phosphines occurs at the carbon-nitrogen double bond. These ketenimines appear to enter into cycloaddition reactions very readily with acetylenes they give quinolines, with nitrones they give oxindoles or oxadiazolidines (see p. 107), i > i and with isocyanides they yield iminoindolenines. These reactions are summarized in Scheme 54. 

Imidazolidines are quite common species, and may be prepared in numerous ways, for example by treatment of a guanidine amidine-thiourea with a 1,2-di-iminium species, or reaction of metallated isocyanides with nitrones, or even by thermolysis of 3-oxazolin-5-ones. The most novel preparation of imidazolidines in 1980 has surely been the work of Coyle et on the... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus, base-induced formation of enolate is followed by Michael addition to the nitroalkene and cyclization of nitronate to furnish the nitro-isocyanide after protonation. Loss of nitrous acid (HNO2) and aromatization then affords the pyrrole ester. 

A plausible reaction sequence that accounted for the formation of a-ketoamides is shown in Scheme 15.33. The condensation of an N-hydroxylmethylamine and an aldehyde gave the nitrone 112, which reacted with an isocyanide to afford the nitrilium intermediate 113. The classic Ugi reaction manifold would lead to the formation of a-acyloxyaminoamide 115 via the imidate intermediate 114. -Elimination of acetic acid under the optimized conditions would afford the a-iminoamide 116, which would then be hydrolyzed to 117. 

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