Sustainable Access to Coumarin Derivatives: Photochemical, Electrochemical, and Biochemical Strategies Beyond Classical and Metal-Based Methods

Abstract

Coumarins are privileged scaffolds in medicinal chemistry, chemical biology, and functional materials, yet their synthesis remains dominated by classical condensations and metal-dependent methods that limit structural diversity and sustainability. This review reframes coumarin construction through energy-driven activation, highlighting photochemical, electrochemical, and biochemical strategies as sustainable alternatives. Visible-light processes enable access to three-dimensional, sp³-rich, and fused architectures that are inaccessible by conventional routes, while electrochemical methods replace stoichiometric oxidants with electrical input under metal-free conditions. Biocatalytic and biosynthetic platforms further extend coumarin synthesis into aqueous, selective, and renewable regimes. Collectively, these paradigms align molecular innovation with modern sustainability and design principles.