Microwave‐Assisted One‐Pot [3+2] Cycloaddition of Azomethine Ylides and 3‐Alkenyl Oxindoles: A Facile Approach to Pyrrolidine‐Fused Bis‐Spirooxindoles

Abstract

An efficient microwave-assisted one-pot method has been developed for the construction of pyrrolidine fused bisspirooxindoles through insitu generated azomethine ylide from decarboxylative condensation of isatins and primary α-amino acids with concomitant [3 + 2] cycloaddition of 3-alkenyl oxindoles. These reactions were effectively accelerated by microwave irradiation in ethanol solvent without any additives or catalyst and enable broad substrate scope, atom-economy, eco-friendly, and good yields. The structure and stereochemistry of pyrrolidine fused bis-spirooxindole ring was unambiguously established by single-crystal X-ray analysis.

Oxyphosphonium Enolate Equilibria in a (4+1)‐Cycloaddition Approach toward Quaternary C3‐Spirooxindole Assembly

“…However, in situ NMR analysis would indicate that the composition of intermediates 10 , 11 , 12 , and 13 en route to benzofuran 2 are temperature and solvent dependent. It is noteworthy that formation of (4+1)‐cycloadducts from the addition of 11 a and 11 b to o ‐QMs requires temperatures below −35 °C to avoid competitive degradation of the o ‐QM [13a] …”

Microwave-assisted decarboxylative reactions: advanced strategies for sustainable organic synthesis

“…A homologous type of decarboxylative annulation reaction was disclosed by Shankaraiah and co-workers, 111 in which the one-pot cycloaddition reaction of α-amino acids 87 , isatins 88 , and 3-alkenyl oxindoles 89 took place to afford pyrrolidine-fused bis-spirooxindoles 90 (Scheme 33). The reaction has a wide substrate scope and excellent tolerance of functional groups with high selectivity.…”

Transition‐Metal‐Free Synthesis of N‐Heterocyclic Compounds via Multi‐Component Reactions

“…Therefore, the development of novel and efficient strategies for synthesizing pyrrolidine derivatives is highly significant. In a study by Bhandari et al., they reported the synthesis of pyrrolidine‐fused bisspirooxindoles 122 using an in‐situ generated azomethine ylide from the decarboxylative condensation of isatins 74 and primary amino acids 120 , along with the concurrent [3+2] cycloaddition of 3‐alkenyl oxindoles 121 through a microwave‐assisted one‐pot approach (Scheme 19) [35] . Initially, the reaction between isatin 74 and primary amino acid 120 formed intermediate 123 which then convert into an insitu generation of reactive azomethine ylide intermediate 124 through oxazolidinone 123'' formation.…”