A Metathesis Model for the Dehydrogenative Coupling of Amines with Alcohols and Esters into Carboxamides by Milstein’s [Ru(PNN)(CO)(H)] Catalysts

Milstein’s [Ru­(PNN)­(CO)­(H)]
catalyst (1-Ru) is known to mediate the dehydrogenative
coupling of alcohols into esters. When it is used in alcohol–amine
mixtures it catalyzes carboxamide formation selectively over esters
and imines. The given chemistry is generally accepted to follow metal–ligand
cooperation (MLC) mechanisms involving hemiacetals and hemiaminals
as intermediates. Using electronic structure DFT methods we investigate
alternative, more direct OR/H and NHR/H metal/acyl metathesis routes
to coupling that circumvent the intermediacy of the hemiacetal and
the hemiaminal. The newly proposed mechanism involves formation of
hemiacetaloxide and hemiaminaloxide ion-pairs by addition of an aldehyde
(from metal-catalyzed alcohol dehydrogenation) to an octahedral ruthenium-alkoxide
or ruthenium-amide intermediate (from alcohol or amine addition to 1-Ru), followed by simple rearrangement (slippage) within
the intact ion-pairs to transfer a hydride from the hemiacetaloxide
or hemiaminaloxide to the metal. We show that the computed potential
energy surfaces that are sometimes invoked to support the MLC mechanism
correspond to indirect routes to metathesis. Both the ion-pair and
the MLC routes predict the dehydrogenative coupling of ethanol and
methanol into methyl acetate to be kinetically much more favored than
the kinetics of formation of N-methylacetamide from
ethanol and methylamine. However, the calculations provide evidence
for the accessibility of a low energy NHR/OR metathesis path that
would amidate the ester into the experimentally observed thermodynamically
more favored carboxamide product. In fact, 1-Ru is known
to be a catalyst for ester amidation.