The inhibition of protein-protein interactions requires molecules of shapes different from established compounds in screening libraries. As the modulation of protein-protein interactions requires inhibitors of larger size, we synthesized trans-imidazoline analogs to the Nutlins, which were reported as a class of potent, non-peptide, small-molecule MDM2 inhibitors recently. We have embarked on a program to synthesize a diversity-oriented library of 2H-imidazolidines, which allows the decoration of the core structure with up to six different residues. The condensation of 1,2-diamines and ketones allowed to control the stereochemistry at C4 and C5. Because these 1,2-diamines are limited commercially available, we applied a second main strategy using a multi-step procedure. This alternative consists of an alkyne synthesis, a 1,2-diketone formation and a Debus-Radziszewski reaction to synthesize the imidazole products. Diaryl-substituted acetylenes were obtained via a copper-free variant of the Sonogashira-reaction in yields up to 97%. Cheap potassium permanganate as the oxidation reagent generated the corresponding 1,2-diketones in yields up to 89% in the second step. The formation of imidazoles via a Debus-Radziszewski multi-component reaction was achieved in high yields. 24 imidazole derivatives were obtained. To obtain alkyl-substituted 1,2-diketones, a different method based on a Au(I)-catalyzed migration of 1,4-bis-propargyl acetates had to be applied. For the subsequent decoration of the scaffold, a reduction the C=N bonds was envisaged as a first step. Using a number of well-known methods, only one of the two double bonds was reduced. For a complete reduction of both C=N bonds, only a Birch reduction was successful. This clean reaction furnished the imidazolidine with almost perfect yield. These 2H-imidazolines served as starting points for further decoration by means of an N-alkylation and N-acylation.