Rapid Assembly of Polyfunctional Structures Using a One-Pot Five- and Six-Component Sequential Groebke-Blackburn/Ugi/Passerini Process

Sequential addition of up to six components under well-defined conditions results in the formation of novel structures with amino acid, peptide, and heterocyclic components. This process forms up to eight new bonds under very mild conditions and tolerates a broad spectrum of functional groups. An orthogonal union of the Groebke-Blackburn three-component reaction with the Ugi four-component or Passerini three component reaction was adopted to synthesize polyfunctionalized heterocycles. In terms of diversity oriented synthesis, 10 positions on the basic polycyclic structure can be varied. Straightforward batch splitting provides a simple and efficient method for preparing structurally complex analogs.