Highly efficient and regioselective synthesis of spirooxindolo pyrrolizidines by reaction of isatin, proline and acrylonitrile/methyl acrylate in water

Decade Advance of Isatin in Three‐component Reactions

“…The core unit of spirooxindolo pyrrolidine 18.1 exists in series of naturally occurring alkaloids such as horsfiline, elacomine and mitraphylline [18a] . The goal of this paragraph is to present a overview of 1,3‐dipolar cycloaddition and its applications for facile synthesis of spirooxindolo pyrrolidines.…”

“…Electron‐deficient alkenes like acrylonitrile, [18a] chalcone, [18b] naphthoquinone, [18c] α, β ‐unsaturated ketones, [18d,e] tetraethyl vinyliden‐ ebis(phosphonate), [18f] azirine, [18g] cyclopropenes, [18h] nitroolefins, [18i,k,l] 3‐nitrochromanes [18i] and maleimide [18m] have been reported. Several literature protocols have utilized environmentally friendly solvents like water, [18a] ethyl lactate, [18c] MeOH, [18b,h,m] EtOH [18d,l] or i PrOH [18k] as the reaction media. Products of these methods exhibited diverse biological properties, such as anti‐inflammatory, [18b] anticancer [18h] activity.…”

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

“…Isatin-derived azomethine ylides were recognized as typical dipoles and generally generated in situ by decarboxylative condensation of α -amino acids with isatins, which then react with dipolarophiles [ 31 ]. Significantly, diverse dipolarophiles have proven highly fruitful, including electron-deficient alkenes (activated by nitro [ 32 , 33 , 34 , 35 , 36 ], carbonyl [ 37 , 38 , 39 , 40 ], or other electron-withdrawing groups [ 41 , 42 , 43 ]), alkynes [ 44 , 45 , 46 ], arylacetylenes [ 47 ], allenes [ 48 ], N -heteroenes [ 49 , 50 ], and strained cyclopropenes [ 51 ]. However, previously reported methods mainly focused on the traditional ‘single target’ approach, and thus, only one type of spirooxindole skeleton can be prepared via the 1,3-dipolar cycloaddition of isatin-derived azomethine ylides to monogroup-activated dipolarophiles.…”

Approaches towards 3‐Substituted‐3‐hydroxyoxindole and Spirooxindole‐Pyran Derivatives in a Reaction of Isatin with Acetylacetone in Aqueous Media

“…Recently, we disclosed synthetic protocols for a series of 3‐hydroxyoxindole and spirooxindole derivatives as a part of our research program directed towards the development of synthetic methodologies involving multicomponent reactions of isatin –. Further to expand our scope of the investigation, we planned to functionalize both C 1 and C 3 position of acetylacetone in a reaction with isatin using water as a reaction media.…”