Pseudo five component reaction towards densely functionalized spiro[indole-3,2′-pyrrole] by picric acid, an efficient syn-diastereoselective catalyst: insight into the diastereoselection on C(sp3)–C(sp3) axial conformation?

Organic & Biomolecular Chemistry Pub Date: 2019-01-10 DOI: 10.1039/C8OB02849D

Abstract

A new series of highly-functionalized spiro compounds of pyrrole were synthesized by a one pot, step-economic condensation of isatin, arylamine and β-keto ester catalyzed by wet picric acid. Initially, the reaction was proposed with an expectation of the formation of a multi-spiro heterocyclic framework of highly-substituted piperidine. However, the isomeric compound was characterized to be a five-membered pyrrole derivative with a diverse scope of variations having different types of substituents in the three components respectively. The possibility of formation of various diastereomers around the hindered single bond and the spiro carbon was limited, as only syn products syn-60 and syn-60′ were isolated in all the reactions performed under the standard conditions. Probably the reactions were mediated by the si-facial formation of the bonds in a picric acid stabilized charge transfer complex transition state. Also, the manner a molecule achieves the most stabilized energy minimized arrangement with all its substituents in space was studied by DFT calculations where syn-60 was more stable than syn-60′. The studies on the formation of syn-60 and syn-60′ were carried out by variation of electronic and steric factors in each of the components of the reactions.

Graphical abstract: Pseudo five component reaction towards densely functionalized spiro[indole-3,2′-pyrrole] by picric acid, an efficient syn-diastereoselective catalyst: insight into the diastereoselection on C(sp3)–C(sp3) axial conformation
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