Multicomponent electron-withdrawing group

Another multicomponent synthesis giving N-3-substituted compounds 28 consisted of the sequential reaction of metallated phosphonoacetates, in one pot, with a nitrile then an aldehyde and finally an isocyanate. This was an extensive study of the scope and limitations of the different substituents on all the components. The most important feature was that, for good yields, the isocyanate should bear an electron-withdrawing group - tosyl was the most successful. However, an exchange reaction could be carried out by reaction of the tosyl products with aryl isocyanates under microwave irradiation, giving the N-3-aryl derivatives 29 <06CEJ7178>. 

K, respectively [5]. These values are three orders of magnitude larger than that for addition to terminal alkenes such as 1-hexene. For this reason, electron-deficient alkenes are frequently employed for multicomponent reactions. However, as the resulting radicals have an electron-withdrawing group they are now electrophilic, and are likely to add to electron-rich alkenes with reasonable rate constants. 

Imidazo[l,2-(j]pyridines can be prepared from a multicomponent reaction of alcohols, 2-aminopyridines, and isocyanides (Scheme 53) (13TL95). The alcohols are oxidized by DMSO and propylphosphonic anhydride, which also catalyzes the nucleophilic addition with isocyanides. Aromatic alcohols with electron-donating and electron-withdrawing groups can provide the desired... 

A multicomponent reaction has also been nsed to generate indoles, pyrazoles, and pyridazinones from arenediazoninm salts (Scheme 3.68) [74]. An inexpensive silver salt served as the catalyst for this transformation. The reaction was generally regioselective and insensitive to the presence of electron-donating or electron-withdrawing groups. The synthesis of linked indoles has also been accomplished nsing this approach (Scheme 3.69). 

Such behavior of amine 213 in [202] was explained by the presence of an intramolecular hydrogen bond and the electron-withdrawing influence of the carboxamide moiety on the nucleophilicity of the amino group. Owing to the formation of intermediates E and F, the reaction products of the multicomponent and sequential processes are identical. 

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