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Scaffold-generating transformations of the Groebke-Blackburn-Bienayme (GBB) reaction products are reviewed. The literature cases were grouped according to the reactions employed as the post-condensational event as follows: lactamization, intramolecular arylation, intramolecular Michael addition, cyclizations involving an alkyne moiety and miscellaneous. Although synthetic strategic based on the post-GBB modifications have been exploited to a lesser extent compared to post-Ugi modifications, the interest of researchers to the GBB reaction as the platform for designing new polycyclic scaffolds has been on the rise in the past decade.

We describe an efficient approach for the synthesis of N-substituted 2-alkenylamides in trifluoroethanol via an Ugi 4-component reaction in short reaction times. The use of a catalytic amount of sulfuric acid in trifluoroethanol gave the desired trifluoroethyl derivatives in good to high yields.

An efficient palladium-catalyzed protocol for the stereoselective synthesis of 3-(aminoarylmethylene)-oxindoles has been developed. In this approach, Ugi-4-component reaction adducts were used as starting materials for carbopalladative cyclization–Buchwald reaction sequences.

An efficient synthesis of tetracyclic uracil derivatives (polycyclic pyrans) is achieved via domino Knoevenagel-hetero-Diels–Alder reactions of O-propargylated salicylaldehyde derivatives with 1,3-dimethylbarbituric acid in water as solvent in the presence of CuI. The products are formed in good yields.

Polyfunctional 1,4-disubstituted piperazines were successfully synthesized stereoselectively via a one-pot, five-component Ugi/nucleophilic addition reaction sequence. Regio- and stereo-selective addition of piperazine to an activated alkyne under catalyst-free conditions and high yields of products are advantages of this method.

A novel and efficient protocol is developed for the synthesis of various spiro-2-amino pyrimidinones via the three-component condensation of alkyl cyanoacetates, guanidinium carbonate and N-substituted 4-piperidinones in ethanol at reflux. High yields, neutral conditions, and short reaction times are advantages of this method.

The one-pot, three-component condensation of benzil, benzonitrile derivatives and primary amines on the surface of silica gel under solvent-free conditions and microwave irradiation provided tetrasubstituted imidazoles in high yields.