Mechanistic Studies of Hydride Transfer to Imines from a Highly Active and Chemoselective Manganate Catalyst

We
introduce a highly active and chemoselective manganese catalyst
for the hydrogenation of imines. The catalyst has a large scope, can
reduce aldimines and ketimines, and tolerates a variety of functional
groups, among them hydrogenation sensitive examples such as an olefin,
a ketone, nitriles, nitro groups, and an aryl iodo substituent or
a benzyl ether. We could investigate the transfer step between imines
and the hydride complex in detail. We found that double deprotonation
of the ligand is essential and excess base does not lead to a higher
rate in the transfer step. We identified the actual hydrogenation
catalyst as a K–Mn-bimetallic species and could obtain a structure
of the K–Mn complex formed after hydride transfer by X-ray
analysis. NMR experiments indicate that the hydride transfer is a
well-defined reaction, which is first order in imine, first order
in the bimetallic (K–Mn) hydride, and independent in rate from
the concentration of the potassium base. We propose an outer-sphere
mechanism in which protons do not seem to be involved in the rate-determining
step, leading to a transiently negatively charged nitrogen atom in
the substrate which reacts rapidly with HOtBu (2-methylpropan-2-ol) to produce the amine. This is based on several
observations, such as no dependency of the reaction rate on the HOtBu concentration, no observable manganese
amide complex, and a high reaction constant in a conducted Hammett
study. Furthermore, hydrogen transfer of the catalytic cycle was experimentally
probed and monitored by NMR with subsequent quantitative regeneration
of the catalyst by H2.