Multicomponent domino imine formation/decarboxylation/1,3 dipolar cycloaddition for the synthesis of spiro-pyrrolizidine oxindoles

Domino reactions are highly efficient processes that lead to the synthesis of complex molecules starting from very simple substrates. This agrees completely with the concept of Green Chemistry, in fact many purification steps, required in step-by-step reactions, can be avoided, decreasing dramatically the required time and operational costs of the methods. Multicomponent domino syntheses have been developed aiming to a low environmental impact and high atom-economical protocols [1]. Oxindoles and pyrrolizines are important heterocyclic motifs found in several natural metabolites and key scaffolds in some potential antitumoral agents [2]. Herein, an innovative synthetic approach for the combination of these two heterocycles is reported, leading to new organic compounds which potentially combine their biological activities. The designed synthetic pathway involves an initial domino imine formation/decarboxylation sequence between readily available proline and cinnamaldehyde [3]. Subsequently, in the presence of dipolarophile, such as α-yilidenoxindoles, a 1,3-dipolar cycloaddition step could occur, affording spiro-pyrrolizine oxindoles in an overall three components triple cascade reaction sequence. The desired compounds were obtained with good yields in an operationally simple and high atom-economical process.