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Updated: Oct 25, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Substrate-Controlled Construction of Spiro-3-Oxoindolines and Eight-Membered-Ring Lactams under Bubbling Air
Xiao Zhang1, Jiahao Zhang2, Dan Mou1
1State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, and School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai200237, China.
Abstract:
A substrate-controlled strategy for constructing spiro-3-oxoindolines and eight-membered-ring lactams from cyclic 2,3-dialkyl-substituted indoles has been developed, employing bubbling air to maximize the gas-liquid interfacial area. When tetrahydrocarbazoles and heteroatom-replaced (O and N) analogues were employed, oxidative rearrangement proceeded smoothly to afford spiro-3-oxoindolines. The reaction solvent DMSO worked as a green and quantitative reductant, avoiding the traditional utilization of a stoichiometric phosphine. Converting to tetrahydrocyclopenta[b]indole derivatives, a selective oxidative C(sp2)-C(sp2) bond cleavage was also illustrated, enabling conversion to eight-membered-ring lactams. The preliminary investigation of flammability and explosion risks, combined with kinetic analysis, provides valuable insights into this oxidation reaction. A selective anti-breast-tumor agent 11b against MCF-7 could be formed in 93% yield via Suzuki coupling.
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