关键词: 有机催化, 对映选择性合成, Knoevenagel/Michael/环合反应, 螺[吲哚啉-3,4-吡咯 [3,4-b]吡啶]

Maleimide, 1,4-DHP and spirooxindole structures are important core scaffolds in various natural products and pharmaceutical molecules which exhibit a wide spectrum of biological activities. Therefore, the combination of these three fragments into one molecule may result in a series of structurally and biologically significant new compounds. Despite the significant developments, to the best of our knowledge till date, the enantioselective reaction of isatins, malononitrile and 3-aminomaleimides has not been reported. We herein first developed the enantioselective synthesis of spiro[indoline-3, 4-pyrrolo [3, 4-b]pyridines] derivatives through an organocatalysed cascade Knoevenagel/Michael/cyclization reaction using a (S,S)-quinine-thiourea derivative. Under the optimized conditions, the three-component reaction of isatins, 3-aminomaleimides, and malononitrile yield the desired heterocycle-fused spirooxindoles in good yields (77-86%) with up to 92% enantiomer excess (ee). The catalyst type and the substrate scope were broadened in this methodology.

Key words: organocatalysis, enantioselective synthesis, Knoevenagel/Michael/cyclization, spiro[indoline-3,4-pyrrolo [3,4-b]pyridines]