Sustainable Pd-Catalyzed Aminations "on Dirty Water"

A new approach to Pd-catalyzed C─N bond formation is disclosed based on observations from Nature, where its use of an "on water" phenomenon allows for variations in its pH and content. By employing highly basic conditions generated from addition of a certain amount of KOH (i.e., the "dirt") to the water, aminations take place quickly. This "on dirty water" approach also provides the needed base, further simplifying reactions. The viscosity of the KOH/water (i.e., 30% KOH) presumably prevents dissolution of the organic coupling partners; hence, base-sensitive groups (e.g., esters, nitriles, etc.) are readily accommodated, thereby broadening the scope of this process. Recycling of this highly basic medium is also illustrated, resulting in a very low complete E-Factor. Several comparisons with recent literature routes are made using not only Pd catalysis, but also with aminations based on earth-abundant metals such as Ni and Cu, which tend to be carried out in various organic solvents. Water-based sequences are also shown, including chemoenzymatic catalysis. Prospects for extending this discovery to several other types of valuable bond formations in synthetic chemistry are also presented.