Synthesis of functionalized dispiro-oxindoles through azomethine ylide dimerization and mechanistic studies to explain the diastereoselectivity

Abstract

We have developed a one-pot synthesis of polycyclic fused dispiro-oxindole derivatives by the [3 + 3]-cycloaddition (dimerization) of azomethine ylide derived from condensation of isatin and proline. The dispiro-oxindole ring system is found at the core of a number of alkaloids, which possess significant biological activity and are interesting, challenging targets for chemical synthesis. We have demonstrated formation of two isomers, cis and trans with variable selectivity depending upon the substitution pattern at the N-atom of isatin moiety arising during this type of dimerization. We could also correlate these diastereoselectivities with DFT calculations. The formation and X-ray crystal structure of the cis isomer in this cycloaddition reaction is reported first time. We also gave clear insight into the mechanism of this dimerization reaction.