A Modified Strategy for Pictet−Spengler Reaction Leading to the Synthesis of Imidazoquinoxalines on Solid Phase

An alternative strategy for Pictet-Spengler reaction involving an N-1 linked aromatic amine of imidazole and aldehydes is described. This is in contrast to a typical Pictet-Spengler reaction, which involves an aliphatic amine attached to the carbon of an activated aromatic nucleus and an aldehyde. Our strategy commences with the nucleophilic replacement of fluorine in resin-bound o-fluoro-nitrobenzoic acid with mono- or disubstituted imidazole, followed by reduction of the nitro group to give an N1 linked aromatic amine of the resin-bound imidazole. This was subsequently treated with an aldehyde in toluene at 80 degrees C and then oxidized in the presence of DDQ to give resin-bound imidazoquinoxalines. Finally, acidolytic cleavage furnished the desired compounds in high yields and purities.