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.