Pyrrolo-dihydropteridines via a cascade reaction consisting of iminium cyclization and O–N Smiles rearrangement

The reactions of 5-pyrrolyl-pyrimidinyloxyacetaldehyde or methyl ketone with primary amines yielded hydroxymethylpyrrolopteridine derivatives via a cascade of iminium cyclization and O–N Smiles rearrangement. The present cascade exhibited a different profile compared to the previously reported ones, which consisted of N–N Smiles rearrangement. Lewis acid (TiCl4) under carefully controlled conditions was employed to suppress the competing formation of imine dimers to give the desired heterocycles. A plausible mechanism involving the iminium cyclization and Smiles rearrangement is proposed. This methodology has been used to generate a series of 6-hydroxymethylpyrrolo[1,2-f]pteridine derivatives with potential biological activities.