A highly efficient and eco-friendly method for synthesis of 1,3-indandione ring-fused 3-oxindoles bearing two contiguous quaternary stereocenters via Aldol reaction in aqueous media（Org. Biomol. Chem., 2015, 13, 601–611） Graphic Abstract ABSTRACT A highly efficient and environmentally benign method for the synthesis of oxindoles featuring two contiguous quaternary carbon centers via Aldol reaction starting from various 3-substituted oxindoles has been established. A wide variety of such featuredmultisubstituted 1,3-indandione ring-fused 3-oxindolescaffolds were obtained smoothly in good yields (up to 98%) employing the most green solvent of water as reaction media. Furthermore, their biological activity has been preliminarily demonstrated by in vitroevaluation againsthuman prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cellsK562 by the MTT-based assays, using the commercially available standard drugs Cisplatin as a positive control. Gratifyingly, compounds 3s, 3u, 3y and 3c′ exhibited the best in vitro inhibitory activity against human leukemia cellsK562, which were almost 2.0, 2.8, 2.5 and 2.2 times the activity than the positive control Cisplatin respectively. 3y was 2.7 times the activity than the positive control Cisplatin on PC-3 cancer cells, and 3s, 3u and 3c′ hadcomparable in vitro inhibitory activity againsthuman prostate cancer cells PC-3 with the positive control Cisplatin. 3s, 3u and 3y had good inhibition ability againsthuman lung cancer cells A549. The resultsindicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads for further biological screenings.