Synthesis of Spiro{pyrrolidine-3,1′-pyrrolo[3,4-c]pyrrole} Basic Framework by Multicomponent 1,3-Dipolar Cycloaddition

The synthesis of complex spiro{pyrrolidine-3,1'-pyrrolo[3,4-c]pyrrole} skeleton employing mild conditions is presented. The order of addition of a primary amine, two equivalents of the corresponding maleimide and finally, the aldehyde is of a paramount importance to obtain these final compounds in very high yields. The mechanism is studied performing very simple tests, the Michael type addition of the amine onto the maleimide being the key step. Interestingly, the hybrid scaffold is prepared by sequential addition of two different maleimides. In addition, a more interesting architecture is prepared through a metathesis reaction between allylic residues bonded in the molecule precursor.We gratefully acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (projects CTQ2016-81893REDT, and RED2018-102387-T) the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, CTQ2016-80375-P, CTQ2017-82935-P and PID2019-107268GB-I00), Generalitat Valenciana (CIDEGENT/2020/058) and the University of Alicante