A Synthetic Iron Model of Carbon-Sulfur Bond Activation by the Nitrogenase-Family Enzyme Methylthio-Alkane Reductase.

The all-iron (FeFe) nitrogenase utilizes a complex iron-sulfur cluster to catalyze the reduction of dinitrogen to ammonia (N2R). Recently, it has been found that methylthio-alkane reductase (mar), which reduces methyl thioalkanes to methanethiol and hydrocarbon fragments, has a structurally similar active site. In this report, we explore the reactivity of a trisphosphine boratrane iron complex ([Fe]), an N2R catalyst, with thioalkanes as a functional model system. Reacting the neutral iron dinitrogen complex ([Fe(N2)]) with dimethyl sulfide (Me2S) yields a 1:1 mixture of iron methyl ([FeMe]) and iron methyl thiolate ([Fe(SMe)]) products. Subsequent protonation forms methane and methanethiol, the products of Me2S reduction by mar. Kinetic studies, including kinetic isotope effects (KIE), pre-equilibrium Van't Hoff parameters, and Eyring analysis, as well as the reactivity with a broad scope of thioalkanes, point to [Fe(SMe2)], formed via an uphill pre-equilibrium with [Fe(N2)] as a key intermediate. In [Fe(SMe2)], the C-S bond strength decreases by 44 kcal mol-1, priming it for bond homolysis. We propose that homolytic C-S bond cleavage occurs with the released alkyl radical being trapped by a second equivalent of iron. Comparisons of N2 and thioalkane reduction by [Fe] suggest similar modes of substrate activation at Fe, namely, backbonding into a π* orbital of N≡N and a C-S σ* orbital of Me2S, setting the substrates up for N-H bond formation and homolytic C-S bond cleavage, respectively.