Direct Synthesis of Coumarin Derivatives from Alkynoic Esters via Dual Organocatalysis

Abstract

An efficient synthetic method for coumarin derivatives was developed using a dual organocatalytic reaction. A combination of p-toluenesulfonic acid monohydrate and piperidine was found to efficiently catalyze the cyclization between salicylaldehydes and alkynoic esters to give various coumarin derivatives in good yield and high selectivity. Mechanistic and kinetic data suggested that the conjugate addition between piperidine and alkynoic esters played a crucial role in the reaction mechanism.

Key words

coumarin - alkynoic ester - organocatalysis - p-toluenesulfonic acid - piperidine - conjugate addition

• References and Notes

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• 36 General Procedure for the Preparation of Representative Compound 3-Acetyl-2H-chromen-2-one (3a) To a solution of salicylaldehyde (1a, 0.5 mmol, 1.0 equiv) and p-toluenesulfonic acid monohydrate (0.05 mmol, 0.1 equiv) in acetonitrile (1.0 mL) was added ethyl 2-butynoate (2b, 0.6 mmol, 1.2 equiv) and piperidine (0.1 mmol, 0.2 equiv). The reaction was stirred at 75 °C for 24 h. The reaction mixture was extracted with EtOAc, washed with brine, and dried over anhydrous Na₂SO₄. The solvent was removed in vacuo. The crude product was purified by flash column chromatography with ethyl acetate/hexane (1:5) as eluent to give the desired product. 3-Acetyl-2H-chromen-2-one (3a) Pale yellow solid; yield: 65.8 mg (70%). ¹H NMR (400 MHz, CDCl₃): δ = 8.44 (s, 1 H), 7.59 (m, 2 H), 7.30 (m, 2 H), 2.66 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 195.5, 159.3, 155.3, 147.5, 134.4, 130.3, 125.0, 124.5, 118.3, 116.7, 30.6 ppm.