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 [(η-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, which is over twice that of the higher catalytic activity of the commercially available catalyst [CpRh(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, [(η-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.