Efficient Nicotinamide Adenine Dinucleotide Regeneration with a Rhodium–Carbene Catalyst and Isolation of a Hydride Intermediate

Regeneration of nicotinamide adenine dinucleotide (NADH) has been the primary interest in the field of enzymatic transformation, especially associating oxidoreductases given the stoichiometric consumption. The synthesized carbene-ligated rhodium complex [(η⁵-Cp*)­Rh­(MDI)­Cl]⁺ [Cp* = pentamethylcyclopentadienyl; MDI = 1,1′-methylenebis­(3,3′-dimethylimidazolium)] acts as an exceptional catalyst in the reduction of NAD⁺ to NADH with a turnover frequency of 1730 h^–1, which is over twice that of the higher catalytic activity of the commercially available catalyst [Cp*Rh­(bpy)­Cl]⁺ (bpy = 2,2'-bipyridine). Offsetting the contentious atmosphere currently taking place over the specific intermediate of the NADH regeneration, this study presents pivotal evidence of a metal hydride intermediate with a bis­(carbene) ligand: a stable form of the rhodium hydride intermediate, [(η⁵-Cp*)­Rh­(MDI)­H]⁺, was isolated and fully characterized. This enables thorough insight into the possible mechanism and exact intermediate structure in the NAD⁺ reduction process.