Synthesis of spiro[oxindole-2,3′-pyrrolidine] derivatives via exo-selective 1,3-dipolar cycloaddition reaction, characterization and DFT investigation

A series of spiro[oxindole-2,3 '-pyrrolidine] derivatives (4a-q) were successfully synthesized via an exo-selective 1,3-dipolar cycloaddition reaction between a stabilized azomethine ylide and various (E)-3-arylidene-1-methylpyrrolidine-2,5-diones. The structures and stereochemistry of the cycloadducts were elucidated through 1D and 2D NMR spectroscopic techniques. The preferred reaction pathway was corroborated by DFT calculations using the B3LYP functional with the 6-31 G (d, p) basis set. The results revealed that the cycloaddition reaction follows a normal electron demand mechanism, where the azomethine ylide acts as the nucleophile and the dipolarophile as the electrophile. The Fukui function analysis favors the regio 2, contradicting the experimental observations while, transition state theory aligns perfectly with the experimental results.