Three-component access to 2-pyrrolin-5-ones and their use in target-oriented and diversity-oriented synthesisElectronic supplementary information (ESI) available: Copies of spectra of all compounds. CCDC 1456952. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra06317a

The Hantzsch-type microwave-assisted, solvent-free sequential three-component reaction between primary amines, β-dicarbonyl compounds and α-bromoesters in the presence of indium trichloride afforded 2-pyrrolin-5-ones, which are difficult to access by alternative methods. Ready access to these compounds allowed their use as synthetic building blocks in a target-oriented project aimed at the synthesis of a compound that had previously been postulated as a candidate for HIV integrase inhibition on the basis of computational studies. The versatility of 2-pyrrolin-5-ones was further verified by their use in a diversity-oriented synthesis context, leading to a library of highly functionalized bispiro compounds. The overall process leading to these compounds involved the generation of six bonds and two cycles over three steps, two of which are multicomponent, and the fully controlled generation of up to four stereocenters, including two quaternary ones. The combination of two multicomponent reactions, i.e. a Hantzsch-type synthesis of 2-pyrrolin-5-ones and a 1,3-dipolar cycloaddition generated complex spirocyclic systems.