Micelle-promoted aqueous synthesis of γ-amino acid derivatives via metal-free photoredox decarboxylative three-component coupling

Abstract

γ-Aminobutyric acid (GABA) analogues are of great value in medicinal chemistry and biomedicine, highlighting the need for efficient, green, and sustainable synthetic strategies. Herein, we report an aqueous visible-light-driven multicomponent reaction for the efficient, economical, and green synthesis of a diverse library of complex GABA analogues, whose scaffolds include α,β-substituents, quaternary carbon/quaternary carbon–fluorine centers, free hydroxyls, amino groups, as well as natural product and pharmaceutically active molecular building blocks. Introducing chiral auxiliaries enables asymmetric synthesis of GABA derivatives, and this scalable method rapidly constructs key scaffolds (γ-lactams, δ-amino alcohols, heteroaromatic amines). This protocol overcomes bottlenecks of limited structural diversity and organic solvent dependence in GABA synthesis. Mechanistically, surfactant CTAB enhances the local concentration of electron-deficient alkenes via electrostatic interactions, boosting the reaction rate, selectivity, and efficiency. This straightforward radical approach provides a less costly, non-toxic alternative to classical photochemistry, offering a new strategy for efficient GABA analogue synthesis.