Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non-Innocent Reaction Medium

In contrast to classic protocols carried out under inert atmospheres with dry volatile organic solvents and often low temperatures, we report that the addition of highly polar organometallic compounds to non-activated imines and nitriles proceeds quickly, efficiently, and chemoselectively with a broad range of substrates at room temperature and under air with water as the only reaction medium, providing secondary amines and tertiary carbinamines with yields up to >99%. The significant solvent D/H isotope effect observed for the on-water nucleophilic additions of organolithiums to imines suggests that the on-water catalysis arises from proton transfer across the organic-water interface. The strong intermolecular hydrogen bonds between water molecules may play a key role in disfavouring protonolysis, which occurs extensively in other protic media such as methanol. This work lays the foundation for reshaping many fundamental s-block metal-mediated organic transformations in water.