Triethanolamine-Catalyzed One-Pot Three-Component Domino Annulation Leading to 4H-Pyrano[3,2-c]coumarins: Catalyst Reusability and Decagram-Scale Synthesis

Abstract

A triethanolamine (TEOA)-catalyzed, one-pot, three-component reaction of 4-hydroxycoumarin, aldehydes, and malononitrile was developed as a highly atom-economic domino protocol for the synthesis of biologically significant 4H-pyrano[3,2-c]coumarins. This cascade sequence proceeds through the successive formation of three new σ bonds (two C—C and one C—O). The protocol exhibited a broad substrate scope and proceeded rapidly and efficiently in methanol at ambient temperature or in water at 85 °C. 4H-Pyrano[3,2-c]coumarins were isolated in 51–95% yields using a simple workup without column chromatography. Sustained TEOA catalytic activity across seven consecutive cycles was demonstrated. Gram- and decagram-scale protocols were elaborated, and the plausible mechanistic pathway was proposed in this study.