Suzuki–Miyaura coupling in a microwave-assisted natural eutectic solvent was studied: optimization by design of experiments with response surface methodology, recycling, exemplification, scale-up, and evaluation with CHEM21 toolkit for a sustainable methodology.

For some years now, eutectic solvents have been seen as an alternative to conventional organic solvents and ionic liquids. When the components are of natural origin, they meet the challenges of green chemistry. Although eutectic solvents are used in many synthetic reactions today, few references reported their use in microwave-assisted reactions. To explore their potential and diversify their applications, Suzuki–Miyaura coupling was studied in eutectic solvents under microwave irradiation. After optimization using a design of experiment based on response surface methodology, the most efficient conditions were found to be betaine: glycerol (1:4, mol mol⁻¹) as eutectic solvent, PdCl₂dppf.CH₂Cl₂ as catalyst, Na₂CO₃ as base, and microwave heating at 129 °C for 15 min. The results showed an increase in reactivity with very rapid reaction kinetics. Furthermore, the catalyst in the eutectic solvent was recycled, and a gram-scale reaction was performed as an example. Finally, this new methodology was evaluated using CHEM21 metrics.