Hydrogen Autotransfer in the N-Alkylation of Amines and Related Compounds using Alcohols and Amines as Electrophiles

The versatility and usefulness of heterogeneous and homogeneous catalysts in the alkylation of amines through the so-called hydrogen autotransfer process was reviewed. Mechanistic studies on the homogeneous iridium-catalyzed alkylation of amines with alcohols have been performed using density functional theory (DFT) calculations. This study showed that the found reaction energetic barriers were consistent with the experimental requirements of elevated temperatures. The first alkylation of amines through an indirect aza-Wittig process was performed using the former iridium source. A similar complex has been used in the alkylation of primary amines with primary and secondary alcohols to give a mixture of products. The use of this strategy of alkylation substitutes the classical ones employing hazardous and expensive alkyl halides, sulfonates, or sulfates and allows a greener process, since the only generated waste is water or ammonia. Moreover, the low molecular weight of wastes makes this synthetic strategy unbeatable as far as the atom efficiency numbers are concerned.