“From cosmetic to catalyst: ascorbyl magnesium phosphate as a green catalyst for the efficient synthesis of bis(indolyl)methanes under mild conditions”

Ascorbyl magnesium phosphate (AMP), a biocompatible and commercially available derivative of vitamin C, is introduced as a green and multifunctional catalyst for the synthesis of bis(indolyl)methanes (BIMs). AMP operates through a cooperative Lewis–Brønsted activation mode, the central Mg 2+ polarizes the aldehyde carbonyl, while the surrounding phosphate–ascorbate framework offers both hydrogen-bond stabilization and mild redox buffering. Under solvent-free heating, microwave irradiation, or methanolic conditions at room temperature (rt), AMP efficiently catalyzes the Friedel–Crafts alkylation of indoles with a wide variety of aromatic and aliphatic aldehydes, affording BIM analogs in yields of up to 96 %. Computational studies reveal that solvent competition, particularly with methanol, plays a key role in controlling substrate access to the Mg 2+ site and modulating the catalytic activity. Moreover, partial solvent evaporation facilitates the transition to a fully activated catalytic regime. This bio-derived catalytic system provides a non-toxic, recyclable, and operationally simple alternative to conventional mineral acids and metal catalysts, highlighting the potential of vitamin-based metal phosphates as sustainable promoters for C–C bond formation and green heterocycle synthesis.