Hydride Transfer from Iron(II) Hydride Compounds to NAD(P)+ Analogues

Iron­(II) hydride complexes of the “piano-stool” type, Cp*­(P-P)­FeH (P-P = dppe (1H), dppbz (2H), dppm (3H), dcpe (4H)) were examined as hydride donors in the reduction of N-benzylpyridinium and acridinium salts. Two pathways of hydride transfer, “single-step H–” transfer to pyridinium and a “two-step (e–/H•)” transfer for acridinium reduction, were observed. When 1-benzylnicotinamide cation (BNA+) was used as an H– acceptor, kinetic studies suggested that BNA+ was reduced at the C6 position, affording 1,6-BNAH, which can be converted to the more thermally stable 1,4-product. The rate constant k of H– transfer was very sensitive to the bite angle of P–Fe–P in Cp*­(P-P)­FeH and ranged from 3.23 × 10–3 M–1 s–1 for dppe to 1.74 × 10–1 M–1 s–1 for dppm. The results obtained from reduction of a range of N-benzylpyridinium derivatives suggest that H– transfer is more likely to be charge controlled. In the reduction of 10-methylacridinium ion (Acr+), the reaction was initiated by an e– transfer (ET) process and then followed by rapid disproportionation reactions to produce Acr2 dimer and release of H2. To achieve H• transfer after ET from [Cp*­(P-P)­FeH]+ to acridine radicals, the bulkier acridinium salt 9-phenyl-10-methylacridinium (PhAcr+) was selected as an acceptor. More evidence for this “two-step (e–/H•)” process was derived from the characterization of PhAcr• and [4H]+ radicals by EPR spectra and by the crystallographic structure confirmation of [4H]+. Our mechanistic understanding of fundamental H– transfer from iron­(II) hydrides to NAD+ analogues provides insight into establishing attractive bio-organometallic transformation cycles driven by iron catalysis.