We have recently reported on several Fe catalysts for N2-to-NH3 conversion that operate at low temperature (−78 °C) and atmospheric pressure while relying on a very strong reductant (KC8) and acid ([H(OEt2)2][BArF4]). Here we show that our original catalyst system, P3BFe, achieves both significantly improved efficiency for NH3 formation (up to 72% for e– delivery) and a comparatively high turnover number for a synthetic molecular Fe catalyst (84 equiv of NH3 per Fe site), when employing a significantly weaker combination of reductant (Cp*2Co) and acid ([Ph2NH2][OTf] or [PhNH3][OTf]). Relative to the previously reported catalysis, freeze-quench Mössbauer spectroscopy under turnover conditions suggests a change in the rate of key elementary steps; formation of a previously characterized off-path borohydrido–hydrido resting state is also suppressed. Theoretical and experimental studies are presented that highlight the possibility of protonated metallocenes as discrete PCET reagents under the present (and related) catalytic conditions, offering a plausible rationale for the increased efficiency at reduced driving force of this Fe catalyst system.

Nitrogen fixation, the six-electron/six-proton reduction of N 2 , to give NH 3 , is one of the most challenging and important chemical transformations. Notwithstanding the barriers associated with this reaction, significant progress has been made in developing molecular complexes that reduce N 2 into its bioavailable form, NH 3 . This progress is driven by the dual aims of better understanding biological nitrogenases and improving upon industrial nitrogen fixation. In this review, we highlight both mechanistic understanding of nitrogen fixation that has been developed, as well as advances in yields, efficiencies, and rates that make molecular alternatives to nitrogen fixation increasingly appealing. We begin with a historical discussion of N 2 functionalization chemistry that traverses a timeline of events leading up to the discovery of the first bona fide molecular catalyst system and follow with a comprehensive overview of d-block compounds that have been targeted as catalysts up to and including 2019. We end with a summary of lessons learned from this significant research effort and last offer a discussion of key remaining challenges in the field.

Recently, heme proteins have been discovered and engineered by directed evolution to catalyze chemical transformations that are biochemically unprecedented. Many of these nonnatural enzyme-catalyzed reactions are assumed to proceed through a catalytic iron porphyrin carbene (IPC) intermediate, although this intermediate has never been observed in a protein. Using crystallographic, spectroscopic, and computational methods, we have captured and studied a catalytic IPC intermediate in the active site of an enzyme derived from thermostable () cytochrome High-resolution crystal structures and computational methods reveal how directed evolution created an active site for carbene transfer in an electron transfer protein and how the laboratory-evolved enzyme achieves perfect carbene transfer stereoselectivity by holding the catalytic IPC in a single orientation. We also discovered that the IPC in cytochrome has a singlet ground electronic state and that the protein environment uses geometrical constraints and noncovalent interactions to influence different IPC electronic states. This information helps us to understand the impressive reactivity and selectivity of carbene transfer enzymes and offers insights that will guide and inspire future engineering efforts.

Substrate selectivity in reductive multielectron/proton catalysis with small molecules such as N, CO, and O is a major challenge for catalyst design, especially where the competing hydrogen evolution reaction (HER) is thermodynamically and kinetically competent. In this study, we investigate how the selectivity of a tris(phosphine)borane iron(I) catalyst, PFe, for catalyzing the nitrogen reduction reaction (NRR, N-to-NH conversion) versus HER changes as a function of acid p K. We find that there is a strong correlation between p K and NRR efficiency. Stoichiometric studies indicate that the anilinium triflate acids employed are only compatible with the formation of early stage intermediates of N reduction (e.g., Fe(NNH) or Fe(NNH)) in the presence of the metallocene reductant Cp*Co. This suggests that the interaction of acid and reductant is playing a critical role in N-H bond-forming reactions. DFT studies identify a protonated metallocene species as a strong PCET donor and suggest that it should be capable of forming the early stage N-H bonds critical for NRR. Furthermore, DFT studies also suggest that the observed p K effect on NRR efficiency is attributable to the rate and thermodynamics of Cp*Co protonation by the different anilinium acids. Inclusion of Cp*Co as a cocatalyst in controlled potential electrolysis experiments leads to improved yields of NH. The data presented provide what is to our knowledge the first unambiguous demonstration of electrocatalytic nitrogen fixation by a molecular catalyst (up to 6.7 equiv of NH per Fe at -2.1 V vs Fc).

Electrocatalytic approaches to the activation of unsaturated substrates via reductive concerted proton-electron transfer (CPET) must overcome competing, often kinetically dominant hydrogen evolution. We introduce the design of a molecular mediator for electrochemically triggered reductive CPET through the synthetic integration of a Brønsted acid and a redox mediator. Cathodic reduction at the cobaltocenium redox mediator substantially weakens the homolytic nitrogen-hydrogen bond strength of a Brønsted acidic anilinium tethered to one of the cyclopentadienyl rings. The electrochemically generated molecular mediator is demonstrated to transform a model substrate, acetophenone, to its corresponding neutral α-radical via a rate-determining CPET.