# Simple and Rapid Microwave‐Assisted Suzuki–Miyaura Cross‐coupling in Betaine/Glycerol Natural Eutectic Solvent

## TL;DR

Researchers developed a fast and eco-friendly method for a common chemical reaction using a natural solvent and microwave heating.

## Contribution

A sustainable microwave-assisted Suzuki–Miyaura coupling in a betaine/glycerol eutectic solvent was optimized and validated.

## Key findings

- The optimal eutectic solvent was betaine:glycerol (1:4) with PdCl2dppf.CH2Cl2 catalyst and Na2CO3 base.
- Microwave heating at 129 °C for 15 min achieved rapid and efficient reaction kinetics.
- The catalyst was successfully recycled, and the method was scaled up to gram-level reactions.

## Abstract

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.

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.© 2025 WILEY‐VCH GmbH