1,3-Dipolar cycloaddition, nitrilium

A mild and greener approach to the synthesis of 1,2,4-triazoles by the dipolar cycloaddition of nitrilimines with nitriles has been reported. The nitrilium intermediates were generated in situ from hydrazonyl chlorides 120 and reacted with the nitriles in a one-pot process. Yields of the 1,3,5-trisubstituted products 121a-o were good in the majority of cases (Equation 37 and Table 20) <2005H(65)1183>. 

The preparation of 2,5-dihydrooxazoles from a-hydroxy ketones, aldehydes and gaseous ammonia is illustrated in equation (165). A derivative of 2,5-dihydrooxazole is obtained by the 1,3-dipolar cycloaddition of benzaldehyde to the nitrilium ylide (306), generated from a-chlorobenzylidene-p-nitrobenzylamine (equation 166). 

We next turned our attention to l,3 diol2u cycloaddition reactions of nitrilium ylides as a direct approach towards the tetrasubstituted imidazole. Nitrilium ylides have been reported to undergo 1,3-dipolar cycloaddition with a number of dipolarophUes including imines.(/2-i6) Thus we reasoned that if the nitrilium yUde 14 could be formed, then reacted with the imine 4 derived from 2-cUoro-pyridinecarboxaldehyde 15, it might provide the desired imidazole (Scheme 3). 

From the results of control experiments, the actual mechanism of the present reaction might be as follows The [5+1] cycloaddition of isocyanide 35a and C,N-cyclic N -acyl azomethine imine 34A first proceeded very quickly to afford 36Aa, whose imin-l,3,4-ozazin-6-one ring was cleaved by TMSCl to generate the corresponding nitrilium intermediate (A, Z = TMS) in Scheme 11.9 in situ. Subsequent 1,3-dipolar cycloaddition between the nitrilium intermediate (A) and an azide ion proceeded to afford the corresponding tetrazole 39. 

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