Partition of the Reactive Species of the Suzuki–Miyaura Reaction between Aqueous and Micellar Environments

[Image: see text] The Suzuki–Miyaura reaction between the aryl halide (1) and the phenyl boronic acid (2), in the presence of the palladium(0) complex (3) as catalyst, gives the cross-coupling product (4) in quantitative yield when performed in basic aqueous solution of the nonionic surfactant Kolliphor-EL (K-EL). The partition between the aqueous and micellar environments of the species of this reaction has been investigated by means of Molecular Dynamics (MD) simulations. Starting from the K-EL molecules dispersed in water, a micelle model has been generated by MD simulations, adopting the 2016H66 force field. Reagent and product species have been described with the same force field, once the reliability of this force field has been tested comparing the n-octanol/water partition free energies calculated from the MD and Free Energy Perturbation (FEP) method with those obtained from the quantum-mechanical SMD method. The potential of mean force for the transfer process between water and the micellar phase of the different species has been calculated by the MD simulations and the Umbrella Sampling (US) method. The overall picture that emerges from these results confirms that the molecular species involved in this reaction prefers the micellar environment and concentrates in different but close zones of the micelle. This supports the experimental evidence that the use of suitable surfactant agents promotes reactivity, allowing micelles to behave as nanoreactors in which reactive species are solubilized and enhance their local concentration.