SEARCH

SEARCH BY CITATION

Keywords:

  • Organocatalysis;
  • Heterocycles;
  • Michael addition;
  • Reduction;
  • Spiroox­ind­oles

Abstract

Heterocyclic spirooxindoles that bear a multisubstitutedheterocyclic motif and quaternary stereocenter at the 3-position are prevalent in a large number of spirooxindole alkaloids, which are pharmaceutically relevant compounds with remarkable biological activities. In this paper, we report an efficient method for the construction of enantiomerically enriched spiro[2H-pyran-3,4′-indoline] derivatives by a systematic Michael/reduction/cyclization sequence. The initial Michael addition of isatylidenemalononitriles with ketones was catalyzed by a cinchona-based chiral primary amine and L-camphorsulfonic acid and furnished multifunctional, optically active Michael adducts in high yields (81–99 %) with excellent enantioselectivities (95 to >99 % ee). Subsequently, the Michael adducts were converted into spiro[2H-pyran-3,4′-indoline] derivatives in 52–93 % yields with 1.5:1 to 20:1 diastereomeric ratio and 90–99 % ee by utilizing NaBH4 as a cascade reduction/cyclization reagent.