A new approach for the synthesis of original substituted pyrrolo-[3,2-c]quinoline derivatives using microwave-assisted chemistry is described. The use of microwave activation in this synthesis resulted in high yielding and clean steps. The key step for introducing diversity is the amination or the Pd-catalyzed cross-coupling of an imidoyl chloride derivative, obtained in a straightforward manner and in good yield.

Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro–Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.