Iridium-Catalyzed Redox-Neutral Alcohol-Amine Coupling on Kilogram Scale

Berliner et al. have reported the first kilogram-scale synthesis of the precursor of a GlyT1 inhibitor, using (Cp*IrCl₂)₂ catalyzed redox-neutral coupling of an alcohol and a substituted benzylamine, a coupling which is generally referred to as a “borrowing hydrogen” reaction. They have demonstrated that the presence of water is essential to keep high catalytic activity, resulting in reaction rates which are dramatically increased on both small and large scales. The reaction has been optimized to achieve catalyst loadings lower than 0.05 mol% iridium while retaining reasonable reaction time.