Mechanistic insights into radical formation and functionalization in copper/N-fluorobenzenesulfonimide radical-relay reactions.

Copper-catalysed radical-relay reactions that employ N-fluorobenzenesulfonimide (NFSI) as the oxidant have emerged as highly effective methods for C(sp3)-H functionalization. Herein, computational studies are paired with experimental data to investigate a series of key mechanistic features of these reactions, with a focus on issues related to site-selectivity, enantioselectivity, and C-H substrate scope. (1) The full reaction energetics of enantioselective benzylic C-H cyanation are probed, and an adduct between Cu and the N-sulfonimidyl radical (˙NSI) is implicated as the species that promotes hydrogen-atom transfer (HAT) from the C-H substrate. (2) Benzylic versus 3° C-H site-selectivity is compared with different HAT reagents: Cu/˙NSI, ˙OtBu, and Cl˙, and the data provide insights into the high selectivity for benzylic C-H bonds in Cu/NFSI-catalyzed C-H functionalization reactions. (3) The energetics of three radical functionalization pathways are compared, including radical-polar crossover (RPC) to generate a carbocation intermediate, reductive elimination from a formal CuIII organometallic complex, and radical addition to a Cu-bound ligand. The preferred mechanism is shown to depend on the ligands bound to copper. (4) Finally, the energetics of three different pathways that convert benzylic C-H bonds into benzylic cations are compared, including HAT/ET (ET = electron transfer), relevant to the RPC mechanism with Cu/NFSI; hydride transfer, involved in reactions with high-potential quinones; and sequential ET/PT/ET (PT = proton transfer), involved in catalytic photoredox reactions. Collectively, the results provide mechanistic insights that establish a foundation for further advances in radical-relay C-H functionalization reactions.

Accessing Ta/Cu Architectures via Metal-Metal Salt Metatheses: Heterobimetallic C-H Bond Activation Affords µ-Hydrides.

We employ a metal-metal salt metathesis strategy to access low-valent tantalum-copper heterometallic architectures (Ta-µ2 -H2 -Cu and Ta-µ3 -H2 -Cu3 ) that emulate structural elements proposed for surface alloyed nanomaterials. Whereas cluster assembly with carbonylmetalates is well precedented, the use of the corresponding polyarene transition metal anions is underexplored, despite recognition of these highly reactive fragments as storable sources of atomic Mn- . Our application of this strategy provides structurally unique early-late bimetallic species. These complexes incorporate bridging hydride ligands during their syntheses, the origin of which is elucidated via detailed isotopic labelling studies. Modification of ancillary ligand sterics and electronics alters the mechanism of bimetallic assembly; a trinuclear complex resulting from dinuclear C-H activation is demonstrated as an intermediate en route to formation of the bimetallic. Further validating the promise of this rational, bottom-up approach, a unique tetranuclear species was synthesized, featuring a Ta centre bearing three Ta-Cu interactions.

The NADH recycling enzymes TsaC and TsaD regenerate reducing equivalents for Rieske oxygenase chemistry.

Many microorganisms use both biological and nonbiological molecules as sources of carbon and energy. This resourcefulness means that some microorganisms have mechanisms to assimilate pollutants found in the environment. One such organism is Comamonas testosteroni, which metabolizes 4-methylbenzenesulfonate and 4-methylbenzoate using the TsaMBCD pathway. TsaM is a Rieske oxygenase, which in concert with the reductase TsaB consumes a molar equivalent of NADH. Following this step, the annotated short-chain dehydrogenase/reductase and aldehyde dehydrogenase enzymes TsaC and TsaD each regenerate a molar equivalent of NADH. This co-occurrence ameliorates the need for stoichiometric addition of reducing equivalents and thus represents an attractive strategy for integration of Rieske oxygenase chemistry into biocatalytic applications. Therefore, in this work, to overcome the lack of information regarding NADH recycling enzymes that function in partnership with Rieske non-heme iron oxygenases (Rieske oxygenases), we solved the X-ray crystal structure of TsaC to a resolution of 2.18 Å. Using this structure, a series of substrate analog and protein variant combination reactions, and differential scanning fluorimetry experiments, we identified active site features involved in binding NAD+ and controlling substrate specificity. Further in vitro enzyme cascade experiments demonstrated the efficient TsaC- and TsaD-mediated regeneration of NADH to support Rieske oxygenase chemistry. Finally, through in-depth bioinformatic analyses, we illustrate the widespread co-occurrence of Rieske oxygenases with TsaC-like enzymes. This work thus demonstrates the utility of these NADH recycling enzymes and identifies a library of short-chain dehydrogenase/reductase enzyme prospects that can be used in Rieske oxygenase pathways for in situ regeneration of NADH.

Synthesis, Structural Characterization, and CO2 Reactivity of a Constitutionally Analogous Series of Tricopper Mono-, Di-, and Trihydrides.

The formation of hydrides at heterogeneous copper surfaces results in dramatic structural and reactivity changes, yet the morphologies of these materials and their respective roles in catalysis are not well understood. Of particular interest is the reactivity of heterogeneous copper hydrides with carbon dioxide (CO2), an early mechanistic branching point in the CO2 reduction reaction. Herein, we report the synthesis, characterization, and reactivity of tricopper compounds supported by a facially biased, chelating tris(carbene) ligand scaffold. This sterically bulky environment affords access to an isolable series of tricopper hydrides: [LCu3H]2+ (4), [LCu3H2]+ (3), and LCu3H3 (6). Single-crystal X-ray diffraction and solution NMR spectroscopy studies reveal both geometric flexibility within the Cu3 core and fluxionality of hydride ligands across the Cu3 cluster, providing both atomically precise experimental analogues of static surface species and emulating dynamic ligand behavior proposed for surfaces. Electronic structure calculations serve as a predictor of hydricity, which was likewise benchmarked experimentally via both protonolysis and hydride abstraction reactions. Increased hydride number (and commensurately lower cluster charge) results in more hydridic complexes, with a thermodynamic hydricity range spanning >30 kcal/mol. These thermochemical studies serve as an accurate predictor of CO2 reactivity. Together, this Cu3Hx series exhibits the structure/reactivity relationships proposed for catalytically active copper surfaces, validating the application of carefully designed molecular clusters toward elucidating mechanisms in surface science.

Molybdenum-Mediated Coupling of Carbon Monoxide to a C3 Product on a Single Metal Site.

The synthesis and characterization of a series of naphthalenediyl-diphosphine molybdenum complexes are reported. A novel dicarbonyl-Mo complex (3) converts to a bis(siloxy)acetylene complex (5) upon reduction and treatment with a silyl electrophile, Me3SiCl. This process shows exclusive C-C coupling distinct from the previously reported phenylene-linked analogue that undergoes C-O cleavage. Further CO catenation can be engendered from 5 under mild conditions providing metallacyclobutenone complex 6, with a C3O3 organic motif derived from CO. Differences in reactivity are assigned to the nature of the arene linker, where the naphthalenediyl fragment shows a propensity for η4 binding previously not observed for phenylene. Consistent with this hypothesis, a Mo precursor with a 1,3-cyclohexadienediyl-based linker was prepared which also showed exclusive formation of a bis(siloxy)acetylene complex and subsequent coupling of a third CO molecule.

Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C-H Coupling with Oxidatively Sensitive Nucleophiles.

Site-selective chlorination of benzylic C-H bonds is achieved using a CuICl/bis(oxazoline) catalyst with N-fluorobenzenesulfonimide as the oxidant and KCl as a chloride source. This method exhibits higher benzylic selectivity, relative to established chlorination protocols, and is compatible with diverse alkyl arenes. Sequential benzylic C-H chlorination/nucleophilic substitution affords C-O, C-S, and C-N coupling products with oxidatively sensitive coupling partners.

Terminal, Open-Shell Mo Carbide and Carbyne Complexes: Spin Delocalization and Ligand Noninnocence.

Open-shell compounds bearing metal-carbon triple bonds, such as carbides and carbynes, are of significant interest as plausible intermediates in the reductive catenation of C1 oxygenates. Despite the abundance of closed-shell carbynes reported, open-shell variants are very limited, and an open-shell carbide has yet to be reported. Herein, we report the synthesis of the first terminal, open-shell carbide complexes, [K][1] and [1][BArF4] (1 = P2Mo(≡C:)(CO), P2 = a terphenyl diphosphine ligand), which differ by two redox states, as well as a series of related open-shell carbyne complexes. The complexes are characterized by single-crystal X-ray diffraction and NMR, EPR, and IR spectroscopies, while the electronic structures are probed by EPR studies and DFT calculations to assess spin delocalization. In the d1 complexes, the spin is primarily localized on the metal (∼55-77% Mo dxy) with delocalization on the triply bonded carbon of ∼0.05-0.09 e-. In the reduced carbide [K][1], a direct metal-arene interaction enables ancillary ligand reduction, resulting in reduced radical character on the terminal carbide (⩽0.02 e-). Reactivity studies with [K][1] reveal the formation of mixed-valent C-C coupled products at -40 °C, illustrating how productive reactivity manifolds can be engendered through the manipulation of redox states. Combined, the results inform on the electronic structure and reactivity of a new and underrepresented class of compounds with potential significance to a wide array of reactions involving open-shell species.

Copper-Catalyzed Functionalization of Benzylic C-H Bonds with N-Fluorobenzenesulfonimide: Switch from C-N to C-F Bond Formation Promoted by a Redox Buffer and Brønsted Base.

A copper catalyst in combination with N-fluorobenzenesulfonimide (NFSI) has been reported to functionalize benzylic C-H bonds to the corresponding benzylic sulfonimides via C-N coupling. Here, we reported a closely related Cu-catalyzed method with NFSI that instead leads to C-F coupling. This switch in selectivity arises from changes to the reaction conditions (Cu/ligand ratio, temperature, addition of base) and further benefits from inclusion of MeB(OH)2 in the reaction. MeB(OH)2 is shown to serve as a "redox buffer" in the reaction, responsible for rescuing inactive Cu(II) for continued promotion of fluorination reactivity.

Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles.

Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with N-fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.

Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering.

Cross-coupling reactions enable rapid, convergent synthesis of diverse molecules and provide the foundation for modern chemical synthesis. The most widely used methods employ sp2-hybridized coupling partners, such as aryl halides or related pre-functionalized substrates. Here, we demonstrate copper-catalysed oxidative cross coupling of benzylic C-H bonds with alcohols to afford benzyl ethers, enabled by a redox-buffering strategy that maintains the activity of the copper catalyst throughout the reaction. The reactions employ the C-H substrate as the limiting reagent and exhibit broad scope with respect to both coupling partners. This approach to direct site-selective functionalization of C(sp3)-H bonds provides the basis for efficient three-dimensional diversification of organic molecules and should find widespread utility in organic synthesis, particularly for medicinal chemistry applications.

CO Coupling Chemistry of a Terminal Mo Carbide: Sequential Addition of Proton, Hydride, and CO Releases Ethenone.

The mechanism originally proposed by Fischer and Tropsch for carbon monoxide (CO) hydrogenative catenation involves C-C coupling from a carbide-derived surface methylidene. A single molecular system capable of capturing these complex chemical steps is hitherto unknown. Herein, we demonstrate the sequential addition of proton and hydride to a terminal Mo carbide derived from CO. The resulting anionic methylidene couples with CO (1 atm) at low temperature (-78 °C) to release ethenone. Importantly, the synchronized delivery of two reducing equivalents and an electrophile, in the form of a hydride (H- = 2e- + H+), promotes alkylidene formation from the carbyne precursor and enables coupling chemistry, under conditions milder than those previously described with strong one-electron reductants and electrophiles. Thermodynamic measurements bracket the hydricity and acidity requirements for promoting methylidene formation from carbide as energetically viable relative to the heterolytic cleavage of H2. Methylidene formation prior to C-C coupling proves critical for organic product release, as evidenced by direct carbide carbonylation experiments. Spectroscopic studies, a monosilylated model system, and Quantum Mechanics computations provide insight into the mechanistic details of this reaction sequence, which serves as a rare model of the initial stages of the Fischer-Tropsch synthesis.

Molecular Mimics of Heterogeneous Metal Phosphides: Thermochemistry, Hydride-Proton Isomerism, and HER Reactivity.

A new series of low-valent dinuclear molybdenum complexes bearing phosphido or phosphinidene bridging ligands was synthesized as a structural model of heterogeneous metal phosphide catalysts. Addition of acid to a monocationic Mo2 -µ-P complex results in phosphide protonation, affording a dicationic Mo2 -µ-PH species. Alternatively, reaction of an isoelectronic Mo2 -µ-P precursor with LiBEt3 H gives a Mo2 H-µ-P complex. Mixing these species, one bearing a Mo-H and the other a P-H bond, results in facile H2 production at room temperature.

Lewis Acid Enhancement of Proton Induced CO2 Cleavage: Bond Weakening and Ligand Residence Time Effects.

Though Lewis acids (LAs) have been shown to have profound effects on carbon dioxide (CO2) reduction catalysis, the underlying cause of the improved reactivity remains unclear. Herein, we report a well-defined molecular system for probing the role of LA additives in the reduction of CO2 to carbon monoxide (CO) and water. Mo(0) CO2 complex (2) forms adducts with a series of LAs, demonstrating CO2 activation that correlates linearly with the strength of the LA. Protons induce C-O cleavage of these LA adducts, in contrast to the CO2 displacement primarily observed in the absence of LA. CO2 cleavage shows dependence on both bond activation and the residence time of the bound small molecule, demonstrating the influence of both kinetic and thermodynamic factors on promoting productive CO2 reduction chemistry.

A Low-Valent Molybdenum Nitride Complex: Reduction Promotes Carbonylation Chemistry.

Toward nitrogen functionalization, reactive terminal transition metal nitrides with high d-electron counts are of interest. A series of terminal MoIV nitride complexes were prepared within the context of exploring nitride/carbonyl coupling to cyanate. Reduction affords the first MoII nitrido complex, an early metal nitride with four valence d-electrons. The binding mode of the para-terphenyl diphosphine ancillary ligand changes to stabilize an electronic configuration with a high electron count and a formal M-N bond order of three. Even with an intact Mo≡N bond, this low-valent nitrido complex proves to be highly reactive, readily undergoing N-atom transfer upon addition of CO, releasing cyanate anion.

Mild electrochemical synthesis of metal phosphides with dibenzo-7-phosphanorbornadiene derivatives: mechanistic insights and application to proton reduction in water.

Transition metal phosphide films were synthesized using a mild electrochemical method. Dibenzo-7-phosphanorbornadiene derivatives (XPA) are introduced as versatile precursors to amorphous metal phosphide electrocatalysts for proton reduction in acidic water. Homogeneous model reactions reveal distinct reactivity between XPA and nickel in different oxidation states, with Ni(0) resulting in NixPy formation.

Terminal Molybdenum Phosphides with d Electrons: Radical Character Promotes Coupling Chemistry.

A terminal Mo phosphide was prepared through the group transfer of both P and Cl atoms from chloro-substituted dibenzo-7λ3 -phosphanorbornadiene. This compound represents the first structurally characterized terminal transition-metal phosphide with valence d electrons. In the tetragonal ligand field, these electrons populate an orbital of dxy parentage, an electronic configuration that accommodates both metal d electrons and a formal M≡P triple bond. Single-electron oxidation affords a transient open-shell terminal phosphide cation with significant spin density on P, as corroborated by continuous wave (CW) and pulse electron paramagnetic resonance (EPR) characterization. Facile P-P bond formation occurs from this species through intermolecular phosphide coupling.

Mechanism of Molybdenum-Mediated Carbon Monoxide Deoxygenation and Coupling: Mono- and Dicarbyne Complexes Precede C-O Bond Cleavage and C-C Bond Formation.

Deoxygenative coupling of CO to value-added C≥2 products is challenging and mechanistically poorly understood. Herein, we report a mechanistic investigation into the reductive coupling of CO, which provides new fundamental insights into a multielectron bond-breaking and bond-making transformation. In our studies, the formation of a bis(siloxycarbyne) complex precedes C-O bond cleavage. At -78 °C, over days, C-C coupling occurs without C-O cleavage. However, upon warming to 0 °C, C-O cleavage is observed from this bis(siloxycarbyne) complex. A siloxycarbyne/CO species undergoes C-O bond cleavage at lower temperatures, indicating that monosilylation, and a more electron-rich Mo center, favors deoxygenative pathways. From the bis(siloxycarbyne), isotopic labeling experiments and kinetics are consistent with a mechanism involving unimolecular silyl loss or C-O cleavage as rate-determining steps toward carbide formation. Reduction of Mo(IV) CO adducts of carbide and silylcarbyne species allowed for the spectroscopic detection of reduced silylcarbyne/CO and mixed silylcarbyne/siloxycarbyne complexes, respectively. Upon warming, both of these silylcarbynes undergo C-C bond formation, releasing silylated C2O1 fragments and demonstrating that the multiple bonded terminal Mo≡C moiety is an intermediate on the path to deoxygenated, C-C coupled products. The electronic structures of Mo carbide and carbyne species were investigated quantum mechanically. Overall, the present studies establish the elementary reactions steps by which CO is cleaved and coupled at a single metal site.

Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site.

Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer-Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon-oxygen bonds and generate carbon-carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl-diphosphine ligand, that activates and cleaves the strong carbon-oxygen bond of carbon monoxide, enacts carbon-carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl-diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site.

Molybdenum catalyzed ammonia borane dehydrogenation: oxidation state specific mechanisms.

Though numerous catalysts for the dehydrogenation of ammonia borane (AB) are known, those that release >2 equiv of H2 are uncommon. Herein, we report the synthesis of Mo complexes supported by a para-terphenyl diphosphine ligand, 1, displaying metal-arene interactions. Both a Mo(0) N2 complex, 5, and a Mo(II) bis(acetonitrile) complex, 4, exhibit high levels of AB dehydrogenation, releasing over 2.0 equiv of H2. The reaction rate, extent of dehydrogenation, and reaction mechanism vary as a function of the precatalyst oxidation state. Several Mo hydrides (Mo(II)(H)2, [Mo(II)(H)](+), and [Mo(IV)(H)3](+)) relevant to AB chemistry were characterized.