Copper-Catalyzed Synthesis of Furo[3,2-c]coumarins and Dihydrofuro[3,2-c]coumarins through a Propargylation/Alkyne Oxacyclization/Isomerization Cascade under Microwave Irradiation

Abstract

A novel copper-catalyzed microwave-promoted propargyl­ation/alkyne oxacyclization/isomerization cascade for the synthesis of 2-methylfuro[3,2-c]coumarins has been developed. This reaction provides furo[3,2-c]coumarins in moderate to good yields (≤82%) from readily available 4-hydroxycoumarins and terminal propargyl acetates as starting materials. Interestingly, by changing the solvent from dimethyl sulfoxide to 1,2-dichloroethane, the isomeric series of 2-meth­ylene-2,3-dihydrofuro[3,2-c]coumarins were obtained in good to acceptable yields (≤85%).

Key words

cascade reactions - coumarins - propargyl acetates - furocoumarins - cyclization

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• 15 Furo[3,2-c]coumarins 3; General Procedure A mixture of 4-hydroxycoumarin 1 (0.48 mmol, 1.2 equiv), propargyl acetate 2 (0.40 mmol, 1.0 equiv), DIPEA (0.40 mmol, 1.0 eq), CuBr (0.02 mmol, 5 mol%), and DMSO (1 mL) was stirred at r.t. for 30 s and then heated at 100 °C for 20 min by microwave irradiation. The mixture was then cooled to r.t., the reaction was quenched with sat. aq NH₄Cl, and the mixture was extracted with CH₂Cl₂. The organic layers were combined, washed with brine, dried (Na₂SO₄), filtered, and concentrated in vacuo. Purification by a flash chromatography (silica gel, hexane–EtOAc) gave the desired product 3.
• 16 2-Methylene-2,3-dihydrofuro[3,2-c]coumarins 4; General Procedure A mixture of 4-hydroxycoumarin 1 (0.48 mmol, 1.2 equiv), propargyl acetate 2 (0.40 mmol, 1.0 equiv), DIPEA (0.40 mmol, 1.0 equiv), CuBr (0.02 mmol, 5 mol%), and DCE (1 mL) was stirred at r.t. for 30 s and then heated at 100 °C for 20 min by microwave irradiation. The mixture was cooled to r.t. and directly purified by flash chromatography (silica gel, hexane–EtOAc) to give the desired product 4.