Mechanism of homogeneous iridium-catalyzed alkylation of amines with alcohols from a DFT study

Abstract

The reaction mechanism for the Ir-catalyzed alkylation of primary amines with primary alcohols has been studied by DFT calculations. The three-step reaction pathway consists of Ir-catalyzed alcohol dehydrogenation to aldehyde, amine-aldehyde condensation to imine, and then Ir-catalyzed imine hydrogenation to amine. The presence of two essentially mirror-image reactions (dehydrogenation of the alcohol and hydrogenation of the imine) makes the reaction intrinsically challenging. The reaction is however shown to favor the product-forming direction because the dehydrogenation of an alcohol via β-H elimination has a lower barrier than the dehydrogenation of an amine. The prediction that amine dissociation is rate determining is consistent with the faster rate experimentally found here for the weakly basic amine TsNH 2. The ancillary carbonate ligand on Ir is shown to be involved in the hydrogen transfer. The two hydrogen atoms eliminated from the alcohol and added to the imine are transferred as H- and H+, the hydride going to and from the metal and the proton to and from the carbonate base. © 2008 American Chemical Society.