Mechanistic questions in aqueous-organic chemistry.

Understanding organic chemistry in water presents challenges distinct from those encountered in conventional organic solvents. Reaction media are usually heterogeneous and contain colloidal objects (micelles and emulsion droplets) and undissolved solids; however, the analytical tools commonly used to study organic reaction mechanisms are often not well suited to such systems or require substantial adaptation deviating from synthetic conditions. As a result, the development and optimization of reactions proceed as though emulsion droplets are a 'magic box', in which progress is identified through inefficient trial-and-error approaches. Here we highlight outstanding mechanistic questions in aqueous-organic chemistry. Through case studies in selectivity control, trial-and-error reaction optimization and surfactant-free systems, we identify key gaps in mechanistic understanding. Finally, using analytical case studies in small-angle X-ray scattering, NMR spectroscopy, dynamic light scattering, cryo-transmission electron microscopy and fluorescence microscopy, we analyse the scope and limitations of current analytical methods in these systems and discuss opportunities for advancing mechanistic insight.