Flow-Chemistry-Enabled Synthesis of 5-Diethylboryl-2,3'-bipyridine and Its Self-Assembly Dynamics.

5-Diethylboryl-2,3'-bipyridine (1), which is inaccessible by conventional batch methods, was synthesized by using a flow microreactor. Compound 1 was obtained as an equilibrium mixture of a cyclic trimer and a cyclic tetramer in solution, the latter of which was crystallized in benzene by vapor diffusion of hexane at 7 °C. The dynamic nature of this system was confirmed by solvent- and concentration-dependent experiments. Notably, the dynamics was verified by using flow NMR spectroscopy, which revealed that the time required to reach equilibrium was influenced by the solvent ratio (<18 s, 24-28 s, and 34-42 s in 2 : 1, 1 : 1, and 1 : 2 mixtures of [D6 ]acetone and C6 D6 , respectively). Compound 1 and 3-[4'-(diethylboryl)phenyl]pyridine (2) exhibited different self-assembly behavior in solution and crystals. Density functional theory calculations suggested that this difference was largely due to enhanced planarity between two consecutive aromatic rings.

Diastereo- and Enantioselective Metathesis Dimerization/Kinetic Resolution of Racemic Planar-Chiral Vinylferrocenes.

Diastereo- and enantioselective kinetic resolution of racemic planar-chiral 1-R-2-vinylferrocenes (rac-1) was attained by the molybdenum-catalyzed asymmetric metathesis dimerization (AMD). Two sequential AMD reactions of rac-1a (R = Br) provided (E)-(S,S)-1,2-di(2-bromoferrocenyl)ethylene in >99% ee, which was converted to (S,S)-1,2-bis[(2-diphenylphosphino)ferrocenyl]ethane (S,S)-5. Planar-chiral bisphosphine (S,S)-5 coordinated to a dichloropalladium(II) fragment in a trans-chelating fashion, which was applied as a chiral ligand in the palladium-catalyzed asymmetric allylic alkylation showing enantioselectivity of up to 90% ee.

Incorporation of an Asymmetric Mo-Fe-S Cluster as an Artificial Cofactor into Nitrogenase.

Nitrogenase employs a sophisticated electron transfer system and a Mo-Fe-S-C cofactor, designated the M-cluster [(cit)MoFe7 S9 C]), to reduce atmospheric N2 to bioaccessible NH3 . Previously, we have shown that the cofactor-free form of nitrogenase can be repurposed as a protein scaffold for the incorporation of a synthetic Fe-S cluster [Fe6 S9 (SEt)2 ]4- . Here, we demonstrate the utility of an asymmetric Mo-Fe-S cluster [Cp*MoFe5 S9 (SH)]3- as an alternative artificial cofactor upon incorporation into the cofactor-free nitrogenase scaffold. The resultant semi-artificial enzyme catalytically reduces C2 H2 to C2 H4 , and CN- into short-chain hydrocarbons, yet it is clearly distinct in activity from its [Fe6 S9 (SEt)2 ]4- -reconstituted counterpart, pointing to the possibility to employ molecular design and cluster synthesis strategies to further develop semi-artificial or artificial systems with desired catalytic activities.

Nitrogen reduction by the Fe sites of synthetic [Mo3S4Fe] cubes.

Nitrogen (N2) fixation by nature, which is a crucial process for the supply of bio-available forms of nitrogen, is performed by nitrogenase. This enzyme uses a unique transition-metal-sulfur-carbon cluster as its active-site co-factor ([(R-homocitrate)MoFe7S9C], FeMoco)1,2, and the sulfur-surrounded iron (Fe) atoms have been postulated to capture and reduce N2 (refs. 3-6). Although there are a few examples of synthetic counterparts of the FeMoco, metal-sulfur cluster, which have shown binding of N2 (refs. 7-9), the reduction of N2 by any synthetic metal-sulfur cluster or by the extracted form of FeMoco10 has remained elusive, despite nearly 50 years of research. Here we show that the Fe atoms in our synthetic [Mo3S4Fe] cubes11,12 can capture a N2 molecule and catalyse N2 silylation to form N(SiMe3)3 under treatment with excess sodium and trimethylsilyl chloride. These results exemplify the catalytic silylation of N2 by a synthetic metal-sulfur cluster and demonstrate the N2-reduction capability of Fe atoms in a sulfur-rich environment, which is reminiscent of the ability of FeMoco to bind and activate N2.

Four-Electron Reduction of Dioxygen on a Metal Surface: Models of Dissociative and Associative Mechanisms in a Homogeneous System.

Two different four-electron reductions of dioxygen (O2) on a metal surface are reproduced in homogeneous systems. The reaction of the highly unsaturated (56-electron) tetraruthenium tetrahydride complex 1 with O2 readily afforded the bis(µ3-oxo) complex 3 via a dissociative mechanism that includes large electronic and geometric changes, i.e., a four-electron oxidation of the metal centers and an increase of 8 in the number of valence electrons. In contrast, the tetraruthenium hexahydride complex 2 induces a smooth H-atom transfer to the incorporated O2 species, and the O-OH bond is cleaved to afford the mono(µ3-oxo) complex 4 via an associative mechanism. Density functional theory calculations suggest that the higher degree of unsaturation in the tetrahydride system induces a significant interaction between the tetraruthenium core and the O2 moiety, enabling the large changes required for the dissociative mechanism.

A dinuclear Mo2H8 complex supported by bulky C5H2tBu3 ligands.

Hydride-bridged transition metal complexes have been found to serve as suitable precursors for the activation of small molecules without the use of reducing agents. In this study, we synthesized a dinuclear Mo2H8 complex supported by bulky C5H2tBu3 (Cp‡) ligands, Cp‡2Mo2H8 (1), from the reaction of Cp‡MoCl4 with KC8 under H2. The hydrides of complex 1 can be replaced with benzene at 60 °C to afford a µ-benzene complex Cp‡2Mo2H2(µ-C6H6) (2).

Metal-Sulfur Compounds in N2 Reduction and Nitrogenase-Related Chemistry.

Transition metal-sulfur (M-S) compounds are an indispensable means for biological systems to convert N2 into NH3 (biological N2 fixation), and these may have emerged by chemical evolution from a prebiotic N2 fixation system. With a main focus on synthetic species, this article provides a comprehensive review of the chemistry of M-S compounds related to the conversion of N2 and the structures/functions of the nitrogenase cofactors. Three classes of M-S compounds are highlighted here: multinuclear M-S clusters structurally or functionally relevant to the nitrogenase cofactors, mono- and dinuclear transition metal complexes supported by sulfur-containing ligands in N2 and N2Hx (x = 2, 4) chemistry, and metal sulfide-based solid materials employed in the reduction of N2. Fair assessments on these classes of compounds revealed that our understanding is still limited in N2 reduction and related substrate reductions. Our aims of this review are to compile a collection of studies performed at atomic to mesoscopic scales and to present potential opportunities for elucidating the roles of metal and sulfur atoms in the biological N2 fixation that might be helpful for the development of functional materials.

Synthesis of Dinuclear Mo-Fe Hydride Complexes and Catalytic Silylation of N2.

Two transition-metal atoms bridged by hydrides may represent a useful structural motif for N2 activation by molecular complexes and the enzyme active site. In this study, dinuclear MoIV -FeII complexes with bridging hydrides, CpR Mo(PMe3 )(H)(µ-H)3 FeCp* (2 a; CpR =Cp*=C5 Me5 , 2 b; CpR =C5 Me4 H), were synthesized via deprotonation of CpR Mo(PMe3 )H5 (1 a; CpR =Cp*, 1 b; CpR =C5 Me4 H) by Cp*FeN(SiMe3 )2 , and they were characterized by spectroscopy and crystallography. These Mo-Fe complexes reveal the shortest Mo-Fe distances ever reported (2.4005(3) Šfor 2 a and 2.3952(3) Šfor 2 b), and the Mo-Fe interactions were analyzed by computational studies. Removal of the terminal Mo-H hydride in 2 a-2 b by [Ph3 C]+ in THF led to the formation of cationic THF adducts [CpR Mo(PMe3 )(THF)(µ-H)3 FeCp*]+ (3 a; CpR =Cp*, 3 b; CpR =C5 Me4 H). Further reaction of 3 a with LiPPh2 gave rise to a phosphido-bridged complex Cp*Mo(PMe3 )(µ-H)(µ-PPh2 )FeCp* (4). A series of Mo-Fe complexes were subjected to catalytic silylation of N2 in the presence of Na and Me3 SiCl, furnishing up to 129±20 equiv of N(SiMe3 )3 per molecule of 2 b. Mechanism of the catalytic cycle was analyzed by DFT calculations.

Synthesis of [Mo3S4] Clusters from Half-Sandwich Molybdenum(V) Chlorides and Their Application as Platforms for [Mo3S4Fe] Cubes.

Triangular [Mo3S4] clusters are known to serve as platforms to accommodate a metal atom M, furnishing cubic [Mo3S4M] clusters. In this study, three [Mo3S4] clusters supported by η5-cyclopentadienyl (CpR) ligands, [CpR3Mo3S4]+ (CpR = C5Me4SiMe3, C5Me4SiEt3, and C5Me4H), were synthesized via half-sandwich molybdenum chlorides CpRMoCl4. In the cyclic voltammogram of the [Mo3S4] cluster having C5Me4H ligands, a weak feature appeared in addition to the [CpR3Mo3S4]0/- redox process, indicating the interaction between [CpR3Mo3S4]- and the [NnBu4] cation of the electrolyte, while such a feature was less significant for the C5Me4SiR3 variants. The [Mo3S4] clusters with bulky C5Me4SiR3 ligands were successfully applied as platforms to accommodate an Fe atom to furnish cubic [Mo3S4Fe] clusters. On the other hand, the corresponding reactions of the less bulky C5Me4H analogue gave complex mixtures.

3-[4'-(Diethylboryl)phenyl]pyridine: Exclusive Crystallization of the Cyclic Tetramer.

The crystallization of 3-[4'-(diethylboryl)phenyl]pyridine (1), which formed a mixture of oligomers in solution with the cyclic trimer as a major component, in acetone at 0 °C afforded a cyclic tetramer that co-crystallized with solvent molecules. Similarly, solutions of compound 1 in toluene at 10 °C and in benzene at 8 °C furnished the cyclic tetramer with the incorporation of toluene and benzene molecules, respectively, thus suggesting that the cyclic tetramer was the minor component. 13 C CP/MAS NMR spectroscopy of precipitates of compound 1 suggested that precipitation from acetone and toluene each afforded mixtures of the cyclic trimer and the cyclic tetramer, whereas precipitation from benzene exclusively furnished the cyclic tetramer. Therefore, it appeared that crystallization readily shifted the equilibrium towards the cyclic tetramer in benzene. The thermodynamic parameters for the equilibrium between these two oligomers in [D6 ]benzene, as determined from a van't Hoff plot, were ΔH°=-8.8 kcal mol-1 and ΔS°=-23.7 cal mol-1 K-1 , which were coincident with previously reported calculations and observations.

Chemical Synthesis of an Asymmetric Mimic of the Nitrogenase Active Site.

The synthetic inorganic chemistry of metal-sulfur (M-S, M = metals) clusters has played an important, complementary role to the biochemical analyses of nitrogenase toward a better understanding of the enzyme active site. The active site of nitrogenase (designated the M-cluster) can be extracted from the protein in a solvent-stabilized form, [(cit)MoFe7S9C] (cit = (R)-homocitrate). One important finding of the extracted M-cluster is its catalytic activity toward the reduction of C1-substrates (CN-, CO, CO2) into C1-C5 hydrocarbons in solution. This catalytic property poses challenges for chemists to reproduce the function with synthetic mimics, not only because of the biochemical interests but also due to the potential significance in green chemistry and catalysis research. In this context, our successful synthesis of an asymmetric Mo-Fe-S cluster, [Cp*MoFe5S9(SH)]3-, is one of the recent important achievements in synthetic M-S chemistry, as this cluster catalyzes the reduction of C1-substrates in a similar manner to the extracted M-cluster. Even though the synthetic protocol for this cluster has been described in the literature, there are plenty of pitfalls for researchers unfamiliar with synthetic M-S chemistry. In this chapter, we provide general precautionary statements and detailed protocols for the synthesis of [Cp*MoFe5S9(SH)]3-, with a brief discussion of the experimental tips based on the authors' experience in both biochemical and synthetic chemical fields.

Cubane-Type [Mo3 S4 M] Clusters with First-Row Groups†4-10 Transition-Metal Halides Supported by C5 Me5 Ligands on Molybdenum.

A synthetic protocol was developed for a series of cubane-type [Mo3 S4 M] clusters that incorporate halides of first-row transition metals (M) from Groups 4-10. This protocol is based on the anionic cluster platform [Cp*3 Mo3 S4 ]- ([1]- ; Cp*=η5 -C5 Me5 ), which crystallizes when K(18-crown-6) is used as the counter cation. Treatment of in situ-generated [1]- with such transition-metal halides led to the formation of [Mo3 S4 M] clusters, in which the M/halide ratio gradually changes from 1:2 to 1:1.5 and to 1:1, when moving from early to late transition metals. This trend suggests a tendency for early transition metals to tolerate higher oxidation states and adopt larger ionic radii relative to late transition metals. The properties of the [Mo3 S4 Fe] cluster 6 a were investigated in detail by using 57 Fe Mössbauer spectroscopy and computational methods.

N2 activation on a molybdenum-titanium-sulfur cluster.

The FeMo-cofactor of nitrogenase, a metal-sulfur cluster that contains eight transition metals, promotes the conversion of dinitrogen into ammonia when stored in the protein. Although various metal-sulfur clusters have been synthesized over the past decades, their use in the activation of N2 has remained challenging, and even the FeMo-cofactor extracted from nitrogenase is not able to reduce N2. Herein, we report the activation of N2 by a metal-sulfur cluster that contains molybdenum and titanium. An N2 moiety bridging two [Mo3S4Ti] cubes is converted into NH3 and N2H4 upon treatment with Brønsted acids in the presence of a reducing agent.

Tracing the 'ninth sulfur' of the nitrogenase cofactor via a semi-synthetic approach.

The M-cluster is the [(homocitrate)MoFe7S9C] active site of nitrogenase that is derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe4S4] clusters concomitant with the insertion of an interstitial carbon and a 'ninth sulfur'. Combining synthetic [Fe4S4] clusters with an assembly protein template, here we show that sulfite can give rise to the ninth sulfur that is incorporated in the catalytically important belt region of the cofactor after the radical S-adenosyl-L-methionine-dependent carbide insertion and the concurrent 8Fe-core rearrangement have already taken place. Based on the differential reactivity of the formed cluster species, we also propose a new [Fe8S8C] cluster intermediate, the L*-cluster, which is similar to the [Fe8S9C] L-cluster, but lacks the ninth sulfur from sulfite. This work provides a semi-synthetic tool for protein reconstitution that could be widely applicable for the functional analysis of other FeS systems.

Synthesis and Characterization of Bioinspired [Mo2 Fe2 ]-Hydride Cluster Complexes and Their Application in the Catalytic Silylation of N2.

The hydride-supported [Mo2 Fe2 ] cluster complex {Cp*Mo(PMe3 )}2 {FeN(SiMe3 )2 }2 (H)8 (2 a; Cp*=η5 -C5 Me5 ) and its [Mo2 Mn2 ] congener 2 b were synthesized from the reactions of Cp*Mo(PMe3 )(H)5 (1) with M{N(SiMe3 )2 }2 (M=Fe, Mn). The amide-to-thiolate ligand-exchange reactions of complex 2 a with bulky thiol reagents (HSR; R=2,4,6-iPr3 C6 H2 (Tip), 2,6-(SiMe3 )2 C6 H3 (Btp)) furnished the corresponding hydride-supported [Mo2 Fe2 ](SR)2 cluster complexes. The [Mo2 Fe2 ] clusters served as catalyst precursors for the reductive silylation of N2 and yielded ≈65-69 equivalents of N(SiMe3 )3 relative to the [Mo2 Fe2 ] clusters. Treatment of complexes 2 a and b with an excess of CNtBu resulted in the formation of dinuclear Mo-Fe and Mo-Mn complexes, which indicated that the [Mo2 M2 ] cores (M=Fe, Mn) split into two dinuclear species upon accommodation of substrates.

[Fe4] and [Fe6] Hydride Clusters Supported by Phosphines: Synthesis, Characterization, and Application in N2 Reduction.

Multiple iron atoms bridged by hydrides is a common structural feature of the active species that have been postulated in the biological and industrial reduction of N2. In this study, the reactions of an Fe(II) amide complex with pinacolborane in the presence/absence of phosphines afforded a series of hydride-supported [Fe4] and [Fe6] clusters Fe4(µ-H)4(µ3-H)2{N(SiMe3)2}2(PR3)4 (PR3 = PMe3 (2a), PMe2Ph (2b), PEt3 (2c)), Fe6(µ-H)10(µ3-H)2(PMe3)10 (3), and (η6-C7H8)Fe4(µ-H)2{µ-N(SiMe3)2}2{N(SiMe3)2}2 (4), which were characterized crystallographically and spectroscopically. Under ambient conditions, these clusters catalyzed the silylation of N2 to furnish up to 160 ± 13 equiv of N(SiMe3)3 per 2c (40 equiv per Fe atom) and 183 ± 18 equiv per 3 (31 equiv per Fe atom). With regard to the generation of the reactive species, dissociation of phosphine and hydride ligands from the [Fe4] and [Fe6] clusters was indicated, based on the results of the mass spectrometric analysis on the [Fe6] cluster, as well as the formation of a diphenylsilane adduct of the [Fe4] cluster.

Reduction of C1 Substrates to Hydrocarbons by the Homometallic Precursor and Synthetic Mimic of the Nitrogenase Cofactor.

Solvent-extracted nitrogenase cofactors can reduce C1 substrates (CN-, CO and CO2) to hydrocarbons in reactions driven by a strong reductant, SmI2 (E0' = -1.55 V vs SCE). Here we show that a synthetic [Et4N]4[Fe6S9(SEt)2] cluster (designated the Fe6RHH-cluster), which mimics the homometallic [Fe8S9C] core of the nitrogenase cofactor (designated the L-cluster), is capable of conversion of C1 substrates into hydrocarbons in the same reactions. Comparison of the yields and product profiles between these homometallic clusters and their heterometallic counterparts points to possible roles of the heterometal, interstitial carbide and belt sulfur-bridged iron atoms in catalysis. More importantly, the observation that a "simplified", homometallic cofactor mimic can perform Fischer-Tropsch-like hydrocarbon synthesis suggests future biotechnological adaptability of nitrogenase-based biomimetic compounds for recycling C1 substrates into useful chemical and fuel products.

Co6 H8 (Pi Pr3 )6 : A Cobalt Octahedron with Face-Capping Hydrides.

A square-planar Co4 amide cluster, Co4 {N(SiMe3 )2 }4 (2), and an octahedral Co6 hydride cluster, Co6 H8 (Pi Pr3 )6 (4), were obtained from metathesis-type amide to hydride exchange reactions of a CoII amide complex with pinacolborane (HBpin) in the absence/presence of Pi Pr3 . The crystal structure of 4 revealed face-capping hydrides on each triangular [Co3 ] face, while the formal CoII2 CoI4 oxidation state of 4 indicated a reduction of the cobalt centers during the assembly process. Cluster 4 catalyzes the hydrosilylation of 2-cyclohexen-1-one favoring the conjugate reduction. Generation of the catalytically reactive Co cluster species was indicated by a trapping experiment with a chiral chelating agent.

Structure and Reactivity of an Asymmetric Synthetic Mimic of Nitrogenase Cofactor.

The Mo nitrogenase catalyzes the ambient reduction of N2 to NH3 at its M-cluster site. A complex metallocofactor with a core composition of [MoFe7 S9 C], the M-cluster, can be extracted from the protein scaffold and used to facilitate the catalytic reduction of CN- , CO, and CO2 into hydrocarbons in the isolated state. Herein, we report the synthesis, structure, and reactivity of an asymmetric M-cluster analogue with a core composition of [MoFe5 S9 ]. This analogue, referred to as the Mo-cluster, is the first synthetic example of an M-cluster mimic with Fe and Mo positioned at opposite ends of the cluster. Moreover, the ability of the Mo-cluster to reduce C1 substrates to hydrocarbons suggests the feasibility of developing nitrogenase-based biomimetic approaches to recycle C1  waste into fuel products.

Interconversion between [Fe4S4] and [Fe2S2] Clusters Bearing Amide Ligands.

Structural conversion of [Fe4S4] clusters into [Fe2S2] clusters has been suggested to be a fundamental process for some O2-sensing proteins. While the formation of [Fe2S2] clusters from synthetic [Fe4S4] clusters has been unprecedented, an all-ferric [Fe4S4](4+) cluster Fe4S4{N(SiMe3)2}4 (1) was found to split in the presence of pyridines, giving [Fe2S2] clusters Fe2S2{N(SiMe3)2}2(L)2 (2, L = pyridines). The structural conversion between [Fe4S4] and [Fe2S2] clusters appeared to be reversible, and the thermodynamic parameters for the equilibrium reactions between 1 + L and 2 were determined. Assembly of two [Fe2S2] clusters was also induced by chemical reductions of Fe2S2{N(SiMe3)2}2(Py)2 (Py = pyridine), and the resultant [Fe4S4] clusters [1](-) and [1](2-) were found to split into two [Fe2S2] clusters by oxidation with [Cp2Fe](+) in the presence of pyridine.