Double-Carrousel Mechanism for Mn-Catalyzed Dehydrogenative Amide Synthesis from Alcohols and Amines

We
study with density functional theory calculations the mechanism
of the original example of a base-metal-catalyzed synthesis of amides
from alcohols and amines. A preliminary proposal of the mechanism
of this reaction was experimentally reported by Milstein and co-workers.
Instead of the proposed reaction mechanism with a hemilabile pincer
amine arm, our DFT calculations describe a facile protocol, where
the catalyst only produces aldehydes from alcohols. Once formaldehyde
is formed from methanol, it reacts with the amine to form a second
alcohol. This new alcohol undergoes the same procedure as methanol
and creates the desired amide through a double-carrousel mechanism.
The rate-determining step in the catalytic aldehyde synthesis corresponds
to the H2 formation. However, in the nonmetal-catalyzed
part of the mechanism, the interaction of formaldehyde with the amine
is also quite kinetically demanding.