Substrate-Controlled Construction of Spiro-3-Oxoindolines and Eight-Membered-Ring Lactams under Bubbling Air Conditions.

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.