N‑Substituted Derivatives of the Azadithiolate Cofactor from the [FeFe] Hydrogenases: Stability and Complexation

Experiments
are described that probe the stability of N-substituted derivatives
of the azadithiolate cofactor recently confirmed in the [FeFe] hydrogenases
(Berggren, G., et al. Nature 2013, 499,
66). Acid-catalyzed hydrolysis of bis­(thioester) BnN­(CH2SAc)2 gives [BnNCH2SCH2]2 rather than azadithiol BnN­(CH2SH)2. Treatment
of BnN­(CH2SAc)2 with NaOtBu generates
BnN­(CH2SNa)2, which was trapped with NiCl2(diphos) (diphos = 1,2-C2H4(PR2)2; R = Ph (dppe) and Cy (dcpe)) to give fully characterized
complexes Ni­[(SCH2)2­NBn]­(diphos).
The related N-aryl derivative Ni­[(SCH2)2­NC6H4Cl]­(diphos) was prepared analogously from
4-ClC6H4N­(CH2SAc)2, NaOtBu, and NiCl2(dppe). Crystallographic
analysis confirmed that these rare nonbridging [adtR]2– complexes feature distorted square planar Ni centers.
The analogue Pd­[(SCH2)2­NBn]­(dppe) was
also prepared. 31P NMR analysis indicates that Ni­[(SCH2)2­NBn]­(dppe) has basicity comparable to typical
amines. As shown by cyclic voltammetry, the couple [M­[(SCH2)2­NBn]­(dppe)]+/0 is reversible near −2.0
V versus Fc+/0. The wave shifts to −1.78 V upon
N-protonation. In the presence of CF3CO2H, Ni­[(SCH2)2­NBn]­(dppe) catalyzes hydrogen evolution
at rate of 22 s–1 in the acid-independent regime,
at room temperature in CH2Cl2 solution. In contrast
to the instability of RN­(CH2SH)2 (R = alkyl,
aryl), the dithiol of tosylamide TsN­(CH2SH)2 proved sufficiently stable to allow full characterization. This
dithiol reacts with Fe3(CO)12 and, in the presence
of base, NiCl2(dppe) to give Fe2[(SCH2)2­NTs]­(CO)6 and Ni­[(SCH2)2­NTs]­(dppe), respectively.