Extremely Fast NADH-Regeneration Using Phosphonic Acid as Hydride Source and Iridium-pyridine-2-sulfonamidate Catalysts

NADH is a very well-known, high-energy, electron and proton carrier, successfully employed as cofactor in many large-scale biotransformation processes catalyzed by oxidoreductase enzymes. Because of its high cost, NADH has to be necessarily regenerated from cheap and affordable raw materials. Herein, we show that the combination of the [Cp*Ir(R-pysa)NO3] (pysa = κ2-pyridine-2-sulfonamidate; R = H, 4-CF3, and 6-NH2) complexes and H-P(O)(OH)2 as hydride source constitutes a top-performing system for the chemical regeneration of NADH. Particularly, the enhanced metal acidity induced by the electron-withdrawing -S(O)2- bridge, between the -NH amide functionality and the pyridine-ring, and the presence of the -NH2 substituent in proximity to the metal are the key factors for obtaining the highest activity ever reported for the chemical regeneration of NADH (TOF up to 3731 h-1, T = 313 K, pH = 6.58 by 0.4 M phosphite buffer), approaching that of enzymes.