NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene (NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-based /3-hydroxyaldehyde has been developed. The ring opening-closure process enables the diastereodi-vergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents (THF or DCE). The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole and alpha,/3-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst. Moreover, four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent. (c) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

The N-heterocyclic carbene-catalysed retro-aldol/aldol cascade reaction allows for the synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters. By simply changing reaction solvents, diastereodivergent synthesis can be achieved. Selective provision of four stereoisomers can be achieved by using different combinations of a chiral secondary amine and a solvent.