Coupling dinitrogen and hydrocarbons through aryl migration.

The activation of abundant molecules such as hydrocarbons and atmospheric nitrogen (N2) remains a challenge because these molecules are often inert. The formation of carbon-nitrogen bonds from N2 typically has required reactive organic precursors that are incompatible with the reducing conditions that promote N2 reactivity1, which has prevented catalysis. Here we report a diketiminate-supported iron system that sequentially activates benzene and N2 to form aniline derivatives. The key to this coupling reaction is the partial silylation of a reduced iron-dinitrogen complex, followed by migration of a benzene-derived aryl group to the nitrogen. Further reduction releases N2-derived aniline, and the resulting iron species can re-enter the cyclic pathway. Specifically, we show that an easily prepared diketiminate iron bromide complex2 mediates the one-pot conversion of several petroleum-derived arenes into the corresponding silylated aniline derivatives, by using a mixture of sodium powder, crown ether, trimethylsilyl bromide and N2 as the nitrogen source. Numerous compounds along the cyclic pathway are isolated and crystallographically characterized, and their reactivity supports a mechanism for sequential hydrocarbon activation and N2 functionalization. This strategy couples nitrogen atoms from N2 with abundant hydrocarbons, and maps a route towards future catalytic systems.

Reduction or “fixation” of N2 is accomplished by a few catalytic systems[3-8] which fully reduce it to ammonia (NH3)[9]. It is difficult to adapt these processes to form C–N bonds from N2, even though a number of compelling functionalizations of N2 are thermodynamically feasible[10]. Efforts to form C–N bonds from N2 generally require reduction of N2 to make it nucleophilic enough to react with carbon electrophiles[11,12]. Notable examples include synthetic cycles for C–N bond formation from Cummins, Sita, Mori, and Schneider[13-17]. A frequent difficulty is the direct reaction of the reducing agents with the carbon electrophiles.

There would be a substantial advantage if N2 could be induced to form a C–N bond with a simple hydrocarbon, without prior functionalization of the hydrocarbon to convert it into an electrophile. Such a strategy would require C–H activation of the hydrocarbon, leveraging the decades of work on oxidative addition of C–H bonds by low-valent transition metal complexes[18]. C–H functionalization to form cross-coupling products is well-known[19], but there are no previous examples of cross-coupling of C–H bonds with the relatively unreactive N2 molecule.

Here, we report an iron complex that couples N2 and unactivated arenes at low temperature, taking advantage of silyl activation of the N2 to produce silylated anilines in a one-pot procedure. The overall strategy (Fig. 1) begins with C–H bond activation of benzene to form a phenyl fragment, which could migrate to N2 upon silylation to form the key C–N bond. To explore the feasibility of this pathway, we converted the iron(II) bromide complex [LFe(μ-Br)]2 (1) into the iron(I) benzene complex LFe(η6-C6H6) (2)[20]. Fig. 2 shows the structure of 2 and illustrates the β-diketiminate ligand L, which controls the coordination environment of iron[21]. Reduction of 2 with KC8 in the presence of 18-crown-6 (18c6) at room temperature led to the isolable, purple iron(0) complex LFe(η4-C6H6)K(18c6) (3-K)[2]. When 2 was reduced instead with Na and 15-crown-5 (15c5) in benzene, the product was the red iron(II) complex LFe(H)(Ph)Na(15c5) (4-Na), in which a C–H bond of benzene is broken to give an iron(II) complex with phenyl and hydride groups on the iron (Fig. S50). Thus, 3-K and 4-Na have isomeric anions (top of Fig. 2A). Mössbauer spectra of solid 3-K and 4-Na (Fig. S23–S25) support the difference, and density functional theory (DFT) studies indicate that the molecules have high-spin electronic configurations (S = 1 for 3-K and S = 2 for 4-Na). This is a rare case of room-temperature C–H activation using a high-spin iron complex[22,23]. Reduction of 2 with Na and 15-crown-5 in toluene similarly gave LFe(H)(Tol)Na(15c5), from activation of the aryl C–H bonds of the solvent. The X-ray crystal structure refined best to a 61:39 mixture of meta and para isomers (Fig. S54).

Fig. 1.

Strategy for converting benzene and N2 into silylated aniline without the use of carbon electrophiles.

Reduction steps are not shown here for simplicity, but are elaborated in Fig. 4 below. Inset: the iron β-diketiminate fragment used in this implementation of the strategy.

Fig. 2.

Activation of benzene.

(a) Reduction of 2 with KC8/18c6 formed 3-K (left) while reduction with Na/15c5 formed 4-Na (right). In THF solvent the cations dissociate, and isomeric anions 3 and 4 are in equilibrium. (b) Conversion of 4-Na to 6-Na occurred spontaneously in 18% yield (top pathway), but gave a higher yield of 75% with the hydride acceptor BPh3 (bottom pathway), suggesting that hydride loss is likely to be the main reaction pathway.

The solution 1H NMR (nuclear magnetic resonance) spectra of 3-K and 4-Na in C6D6 showed a few peaks that disappeared over several hours, suggesting that these benzene or phenyl groups exchange with C6D6. Additionally, a minor component was observed in the 1H NMR spectrum of the C6D6 solutions of 3-K that resembled those of 4-Na, and vice versa. These observations suggested that arene-bound iron(0) complex 3 and C-H activated iron(II) complex 4 are in equilibrium with one another, and the iron(0) arene isomer (3) predominates with K(18c6)+, while the oxidatively added iron(II) phenyl hydride isomer (4) predominates with Na(15c5)+ (see Tables S7–S8). This hypothesis was strongly supported through solution studies in THF (tetrahydrofuran), a solvent that can disrupt the interactions with the alkali metal. Dissolving either purified 3-K or purified 4-Na in THF gave mixtures with characteristic peaks of both isomers 3 and 4 in 1H NMR and Mössbauer spectra (Fig. S9, S26). The ability of each isomer to produce the other one demonstrates that there is reversible oxidative addition of the aryl C–H bond of 3 to form 4.

Purple THF solutions of LFe(H)(Ph)Na(15c5) (4-Na) turned green upon standing at room temperature for several hours, and 1H NMR spectra showed formation of the iron(I) phenyl complex [LFePh][Na(15c5)] (6-Na) (Fig. 2B). Though the formation of 6-Na from 4-Na corresponds to formal loss of H•, the spectroscopic yield of 6-Na from 4-Na in THF was only 18% (Fig. S17), and the best yield of 6-Na (44%) came from addition of excess 15c5 and Na to 2 in diethyl ether (Fig. S18). These results suggested that the reaction could have a different pathway. In a mechanistically revealing experiment, 4-Na transferred the hydride to BPh3 (triphenylborane) to give 5 and [Na(15c5)][HBPh3] (Fig. S19–S20) in a higher yield of 75%. Therefore, it is possible that in the presence of excess reducing agent, 4-Na can similarly lose hydride to give 5, which is subsequently reduced by 3 or by Na to give the observed 6-Na.

Next, we explored N2 binding. Cooling a solution of 6-Na in THF under an atmosphere of N2 led to changes in the electronic absorption (UV-vis) spectrum (Fig. 3A) and Mössbauer spectrum (Fig. 3B) that did not occur in control experiments under argon. Van’t Hoff analysis of the UV-vis data for 6-Na gave ΔH = −17 ± 2 kJ mol−1 and ΔS = −55 ± 10 J K−1 mol−1 (Fig. S40), which are consistent with the binding of N2. In order to gain crystallographic verification of N2 binding, we cooled a concentrated sample of the potassium analogue 6-K at −78 °C for 3 h, which led to crystals of the N2 complex 7-K. The X-ray crystal structure of 7-K (within Fig. 4 below) demonstrates end-on binding of the N2 unit and a pseudotetrahedral geometry at the iron(I) site, and the spectroscopic similarity to the Na system (Figs. S36–S39) indicates that 7-Na has a similar structure.

Fig. 3.

Binding and functionalization of N2.

(a) Electronic absorption spectra of 6-Na in THF solution at various temperatures under 1 atm N2, demonstrating the formation of 7-Na at lower temperature. The data for 6-K are similar (Fig. S37). (b) 57Fe Mössbauer spectra at 80 K, from samples of 6-K in THF solution frozen under 1 atm Ar (top) or 1 atm N2 (bottom), demonstrating the formation of a new doublet attributed to the N2 complex 7-K (green subspectrum) in addition to some remaining 6-K (red subspectrum). (c) Illustration of the equilibrium of 6 and N2 to form 7. In a key transformation, silylation of the bound N2 in 7 induces migration of the phenyl group to the N2 fragment, giving 8. When a bulkier silyl group is used, it is possible to isolate the singly silylated species 9, which can subsequently form C–N bonds. Each of the iron species has been characterized through X-ray crystallography (Fig. 4 and S50–S55).

Fig. 4.

Proposed cyclic reaction mechanism for the conversion of N2 and benzene to aniline mediated by iron β-diketiminate complexes.

Thermal ellipsoid plots of the isolated intermediates are shown on the outside of the cycle (for ionic compounds, only the anion is shown). Hydrogen atoms and isopropyl groups are omitted from the thermal ellipsoid plots for clarity.

Next, we silylated the N2 ligand that had been activated through Fe coordination. Treating a cold solution of 7-K with 2 equivalents of Me3SiX (X = Br, I) formed the hydrazido complex LFe(N(Ph)N(SiMe3)2) (8). To our knowledge, the transformation of 7 to 8 is the first crystallographically-verified example of the migration of a hydrocarbyl group from a metal to the α position of N2[25-26]. This is the key C–N bond forming step during the formation of silylated anilines (Fig. 1), which differs from the previously utilized attacks on bound N2 by carbon electrophiles.

Though we did not detect any intermediates during the conversion of 7 to 8, the treatment of a cold solution of 7-K with 0.5 molar equivalents of the bulkier triisopropylsilyl triflate (TIPSOTf; OTf = SO3CF3) gave the formally iron(II) diazenido complex 9, in which the N2 is singly silylated while the phenyl group remains bound to the iron (Figure S55). The conversion of 7 to 9 is accompanied by a similar yield of the iron(II) complex 5, which results from half of 7 acting as a reducing agent. Considering this stoichiometry, the formation of 9 occurs in 67% yield. The isolation of 9, in which the phenyl has not migrated, suggests that the initial silylation of the β position of the coordinated N2 in 7 takes place before the migration of the aryl group. It is likely that the second silylation induces the aryl migration, because Peters recently reported the migration of H from an iron center to the α position of a doubly silylated N2 group to form an iron disilylhydrazido complex[27]. Accordingly, addition of excess trimethylsilyl triflate (Me3SiOTf) and excess Na to 9 gave a 14% yield of PhN(SiMe3)2, showing that addition of a second silyl group can initiate C–N bond formation. This could be because the second silylation leads to a formally iron(IV) complex with a Fe=N double bond, a migration that is reminiscent of alkyl migration to N in an imidoiron(IV) complex[28].

The conversion of 8 to the silylated aniline and amine occurred upon the addition of 1 equivalent of KC8 and 2 equivalents of Me3SiX (X = Br, I) to solutions of 8: this treatment led to mixtures containing PhN(SiMe3)2, PhN(SiMe3)N(SiMe3)2 and N(SiMe3)3 within 30 min, either at room temperature or at −100 °C. In contrast, 8 did not react with 2 equivalents of Me3SiBr alone within 3 days at room temperature. This result suggests that reduction precedes the electrophilic attack of silyl groups on 8, and alternatively this final step could involve the formation of Me3Si• radicals[28,30]. Others have also studied the reductive silylation of disilylhydrazido complexes[30,31].

After release of the silylated nitrogen products from 8, the large excess of bromide is expected to give iron(II) bromide species that are poised to be reduced with further arene binding. This suggests the feasibility of a cyclic process (Fig. 4) in a single pot, which forms silylated anilines from arenes and N2. However, the C–H activation and hydride loss to reform complex 6 requires room temperature treatment with Na, and at this temperature Na degrades Me3SiBr. Further, N2 binds to 6 at low temperatures. Thus, we treated 8 with Na (25 equivalents), benzene (20 equivalents), Me3SiBr (6 equivalents), and 15c5 (5 equivalents) at −100 °C in diethyl ether, then warmed to room temperature for 1 h, then cooled again and treated with additional Me3SiBr (6 equivalents). This led to a 92% yield of PhN(SiMe3)2 and a 135% yield of N(SiMe3)3 (yields vs. Fe). In order to verify that the overall process is indeed cyclic, 8 was treated with the same conditions with added toluene in place of benzene. Analysis of the organic reaction products after two cycles of Me3SiBr addition showed a 163% yield of N(SiMe3)3, a 62% yield of PhN(SiMe3)2, and a 16% yield of (tolyl)N(SiMe3)2 (both meta and para isomers). The ability of the phenylhydrazido complex to give products from toluene amination demonstrates that the iron containing products of the hydrazido reduction can activate toluene and continue to another reaction cycle, though the yields are low.

To test the overall cycle, we reacted the easily-prepared iron(II) complex 1 with 30 molar equivalents (equivalents relative to [Fe]) of Na, 20 equivalents of C6H6, and 5 equivalents of 15c5 at ambient temperature in diethyl ether, followed by addition of 6 equivalents of trimethylsilyl bromide (Me3SiBr) at −108 °C, afforded PhN(SiMe3)2 in a yield of 24% per iron atom as determined by gas chromatography (GC). The yield of the reaction could be increased by adding the Me3SiBr in several portions with temperature cycling. First, a mixture of 1, 35 equivalents of Na, 20 equivalents of benzene, and 5 equivalents of 15c5 in diethyl ether was stirred vigorously for 1.5 hours at room temperature until it became green, corresponding to the color of 6. Cooling the mixture to −108 °C under 1 atm N2 resulted in a color change to dark red, corresponding to 7. Then, addition of 2 equivalents of Me3SiBr (per iron) to this cold solution and warming to room temperature for 1 hour resulted in another green reaction mixture, suggesting that 6 was regenerated. Cooling again caused the same color change to red (7), and more Me3SiBr was then added in a second cycle. Repeating 10 cooling/silylation/warming cycles with 2 equivalents of Me3SiBr per cycle gave a cumulative yield of 85 ± 14% of PhN(SiMe3)2 (vs. Fe; average and standard deviation of 6 trials; Table S1). The ability to produce more product with repeated Me3SiBr additions suggests a cyclic process, albeit one where a significant amount of the active species decomposes in each cycle. Though aniline formation was attenuated with repeated cycles, the yield of N(SiMe3)3 continued to increase with the number of additions of Me3SiBr, reaching 380 ± 41% (vs. Fe) (Fig. S1–S2). Under the same conditions but in the absence of benzene, no PhN(SiMe3)2 was produced yet a similar catalytic yield of N(SiMe3)3 was observed. Neither product was detected in the absence of 1. These results suggest that the iron decomposition products lose the ability to aminate benzene, but remain competent for the silylation of N2 to N(SiMe3)3, a more common reaction that has been reported with other homogeneous catalysts and decomposition products[32-40].

Isotope labeling experiments were used to verify that the aniline product arises from benzene and N2. When performing the reaction under an atmosphere of 15N2, GC-MS indicated the formation of Ph15N(SiMe3)2 and 15N(SiMe3)3 (Fig. 5A), demonstrating that N2 is the source of the N atoms. Performing the reaction with C6D6 as the arene substrate gave (C6D5)N(SiMe3)2, showing that benzene is the source of the phenyl group. The reaction with an equimolar mixture of C6H6 and C6D6 gave a 1:1 mixture of (C6H5)N(SiMe3)2 and (C6D5)N(SiMe3)2 (Fig. 5B), but partially deuterated 1,3,5-d3-benzene gave (C6H2D3)N(SiMe3)2 and (C6H3D2)N(SiMe3)2 in a ratio of 2.01 ± 0.05 indicating a normal primary kinetic isotope effect for the C–H cleavage step. The difference between the intramolecular vs. intermolecular isotope effects[41] indicates that arene binding/exchange is not much more rapid than the irreversible step after C–H cleavage, which is qualitatively consistent with the timescales of the experiments described above with the 3/4 equilibrium (which is established over 1–2 hours in diethyl ether) and the formation of 6 (which takes a few hours).

Fig. 5.

Aniline products from amination of arenes with N2.

(a) Mass spectra of PhN(SiMe3)2 products from reaction under 1 atm of natural abundance N2 (top) and from reaction under 1 atm of 15N2 (bottom), showing that the nitrogen atom in the product derives from N2. (b) Yields (relative to Fe) of N-containing products during N2-based amination of different arenes, using 5 cycles of Me3SiBr addition (2 equivalents per cycle).

Other arene substrates were also tested using 5 cycles of Me3SiBr addition (Fig. 5C), conditions under which the yield of benzene to PhN(SiMe3)2 was 68 ± 4% per iron. Toluene gave a mixture of (m-tolyl)N(SiMe3)2 and (p-tolyl)N(SiMe3)2 in a 3:1 ratio with a total yield of 61 ± 7% per iron. The overall yield is similar to that for benzene, and the ratio of isomers is comparable to that observed in the crystal of LFe(H)(Tol)Na(15c5) (Fig. S54). When o-xylene was used, a 12 ± 2% yield of N,N-bis(trimethylsilyl-3,4-xylidine) was observed. These silylated aniline products could be hydrolyzed to the deprotected anilines with weak aqueous acid when desired. Arenes with easily reducible functionalities such as aryl halides, aryl ethers, and polycyclic aromatics did not give aminated products. Formation of the silylated aniline and N(SiMe3)3 also occurred with other Me3SiX reagents as well (X = Cl, I, and OTf), though the reaction gave the highest yields with Me3SiBr.

The strategy outlined here differs fundamentally from previously described strategies for formation of C–N bonds from N2. Typically, carbon electrophiles have been used to create C–N bonds, either from N2[13,42-46] or nitrides that result from cleavage of N2[15-17,47]. In the new reaction, silylation plays a key role by making the coordinated N2 sufficiently reactive to accept the migrating aryl group from the metal center. The silylated amines that are formed can be used in further synthetic steps or can be deprotected to the parent anilines using mild aqueous acid. In this method, the C–N bond comes from the migration of a hydrocarbyl from a metal to an N2-derived group, a strategy that has been used in few stoichiometric C–N bond formation reactions[18,48]. The ability of these iron complexes to generate a hydrocarbyl group on the iron through C–H activation and then transfer it to an activated N2 provides a new tactic for coupling hydrocarbons to N atoms from atmospheric N2, combining the powers of these bond-cleaving reactions.