Transition-Metal-Free Divergent Cyclization of Ynamides with Indolones

A transition-metal-free divergent cyclization of ynamides with indolones is presented, enabling the efficient synthesis of spiroindolones and indole-fused seven-membered rings.The site-selective cyclization can be controlled by different reaction conditions.Under base-promoted conditions, the C3-spirocyclization of 2-indolones takes place and affords spiroindolones.In the presence of acid catalyst, the selective O-cyclization of 2-indolones occurs to give indole-fused sevenmembered ring products.The notable features of this selective cyclization include readily available catalysts and reagents, simple procedure, mild reaction conditions and broad substrate scope.This research provides a practical pathway for the construction of potentially useful spiroindolones and indole-fused seven-membered rings.Accordingly, K2CO3 (2 equiv., 0.4 mmol, 55.3 mg) was added to the solution of ynamide 1 (1 equiv., 0.2 mmol) in MeOH (4 mL) at room temperature.The reaction mixture was then stirred at 60 and the progress of the reaction was monitored by thin layer chromatography (TLC).Upon completion, the mixture was concentrated and purified by chromatography on silica gel (eluent: petroleum ether/ethyl acetate, VV31), to afford the desired spiroindolone 2. Furthermore, A3 (10 mol%, 0.02 mmol, 9.6 mg) was added to the solution of ynamide 1 (1 equiv., 0.2 mmol) in 1,2-dichloroethane (DCE) (4 mL) at room temperature.The reaction mixture was then stirred at 70 and the progress of the reaction was monitored by TLC.Upon completion, the mixture was concentrated and purified by chromatography on silica gel (eluent: petroleum ether/ethyl acetate, VV51), to afford the desired indole-fused seven-membered ring product 3. Also, a possible reaction mechanism involving the selective cyclization is proposed based on experimental results.