Enantioselective Assembly of Spirocyclic Oxindole-dihydropyranones through NHC-Catalyzed Cascade Reaction of Isatins with N-Hydroxybenzotriazole Esters of α,β-Unsaturated Carboxylic Acid

Abstract

An NHC-catalyzed formal [4 + 2] reaction of isatins with N-hydroxybenzotriazole ester of α,β-unsaturated carboxylic acids bearing γ-H to construct spirocyclic oxindole-dihydropyranones featuring a chiral tetrasubstituted carbon stereogenic center was developed. The high enantioselectivity, the ready availability of the raw materials, the facile assembly, and the potential biological significance of the final products make this protocol an attractive alternative for the synthesis of spirocyclic heterocycles.

New development in the enantioselective synthesis of spiro compounds

“…178 The reaction comprises thiol addition to the imine, followed by hemiaminal formation 329 between the resulting amine and the aldehyde and PCC oxidation of hemiaminal 329. 182 Almost simutaneously, Yao reported a similar reaction starting with saturated acids and isatins using NHC as the catalyst. 183 This was followed by the addition of the NHC catalyst to the in situ-formed activated ester (using HATU).…”

Enantioselective Synthesis of Cyclic α‐Aminophosphonates through N‐Heterocyclic Carbene‐Catalyzed [4+2] Annulation of Enals with α‐Iminophosphonates

“…The addition of the NHC to the enal affords the Breslow intermediate I , which is oxidized by the diquinone to afford the unsaturated acyl azolium intermediate II . The dienolate III is generated from intermediate II via γ‐deprotonation in the presence of base ,,,,. Nucleophilic addition of the dienolate to α‐iminophosphonate affords adduct IV , which subsequently undergoes lactamization to furnish the final cycloadduct 3 and regenerates the NHC catalyst.…”

Katalyse durch N‐heterocyclische Carbene über Azoliumdienolate: eine effiziente Strategie für enantioselektive Funktionalisierungen an entfernten Positionen

“…Yao et al. beschrieben 2015 die NHC‐vermittelte Bildung von VI aus α,β‐ungesättigten 1‐Hydroxybenzotriazol(HOBt)‐Estern 35 mit γ‐ständigen Wasserstoffatomen (Schema ) . Die aus dem Acylazolium‐Intermediat 36 erhaltenen Azoliumdienolate VI reagierten in [4+2]‐Cycloadditionen mit 11 zu den Spirooxindolderivaten 12 mit guten bis hohen ee ‐Werten.…”