Transition-metal-catalyzed [2＋2＋2] cycloaddition of alkynes with carbonyl compounds is an efficient way for the synthesis of diverse heterocyclic compounds. However, most of the established methods rely on the noble metal catalysts and are confined to the cyclometallation pathway. Herein, we report a copper-catalyzed [2＋2＋2] cycloaddition of 1,6-diynes with ketones through vinyl cations, enabling the efficient and practical synthesis of a series of biologically important 3-acylindole frameworks in moderate to excellent yields. The cyclization features advantages including readily available catalysts and reagents, simple procedure, mild reaction conditions and broad substrate scope. Particularly, this protocol represents the first construction of this useful framework via transition-metal-catalyzed [2＋2＋2] cycloaddition of diynes with ketones. Accordingly, Cu(CH₃CN₄)PF₆ (0.04 mmol), NaBAr^F₄ (0.048 mmol) and L1 (0.048 mmol) were introduced into an oven-dried vial under N₂ atmosphere. After CH₂Cl₂ (4 mL) was injected into the vial, the reaction mixture was stirred at room temperature under the N₂ atmosphere for 2 h. Then, the corresponding diyne 1 (0.2 mmol) and ketone 2 (1 mmol) and CH₂Cl₂ (4 mL) were added to the reaction mixture. The resulting mixture was stirred at room temperature for 3~37 h and the progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion, the resulting mixture was concentrated under reduced pressure and purified by column chromatography on silica gel (eluent: petroleum ether/ dichloromethane, V∶V=2∶1) to afford the desired indole-2-en-3-arylketone 3. Also, a possible reaction mechanism involving the cascade cycloaddition/ring-opening is proposed based on experimental results.

Key words: diynes, copper catalysis, carbonyl compounds, [2＋2＋2] cycloaddition, 3-acylindole derivatives