Iron-borane catalyzed carbonyl hydroboration and isolation of an iron(I)-ketyl radical

Domain: chemistry
Published: 2026-02-19
Editorial outcome: major_revision

Abstract
Hydroboration of carbonyl compounds has proven a pivotal route to access alcohols and other C1 moieties in recent years. Despite this, iron-based catalyst systems are somewhat limited with very little mechanistic understanding of these systems developed. Here we show that an iron metalloborane complex [{(iPrDPBPh)Fe} (μ−1,2-N )](A) is an efficient pre-catalyst for hydroboration of ketones, cyclic esters and CO with mild conditions. Mechanistic insights reveal a previously unreported direct iron(0)-mediated ligand-to-ligand hydride transfer (LLHT) process is in operation with B–H bond breaking being rate determining, indicating the importance of mechanistic studies on well-known transformations. An iron(I)-benzophenone ketyl radical with a unique S=1 antiferromagnetic ground state has been isolated and fully characterized.

Introduction
Alcohols are privileged structural motifs, which have found widespread application in the pharmaceutical, cosmetic, fragrance and agrochemical industries1–3. To date, the industrial route to simple alcohols involves the reduction of a carbonyl compound in the presence of either hydrogen gas at elevated pressure or the use of other alcohols in transfer hydrogenation processes4–7. Beyond ketones and other simple carbonyl-containing molecules, carbon dioxide can also be efficiently reduced to C1 hydrocarbons, formaldehyde, formic acid and methanol. These products serve as valuable building blocks for the synthesis of fine and commodity chemicals. While traditionally, hydrogenation of CO remains the most atom-efficient route, it necessitates harsh reaction conditions. In the search for milder conditions, homogeneous catalytic hydroboration represents a valuable strategy for the synthesis of alcohols. This two-step process proceeds via the addition of a B–H bond to a carbonyl group to generate a boryl ether that, after hydrolysis, furnishes the desired alcohol8–11. Catalysts derived from s-block12–19, transition metals20–29, p-block30–39, and f-block40–44 element complexes have been employed in this transformative process. However, reports that employ iron-based catalysts are somewhat limited.

In 2017, the group of Findlater reported the first room temperature hydroboration of carbonyl compounds with 10 mol% of Fe(acac) in the presence of NaHBEt as an activator45. The group of Zhang demonstrated the hydroboration of aldehydes and ketones facilitated by an iron(II) coordination polymer, under aerobic conditions28. The Fe O -nanoparticle catalyzed hydroboration of ketones and aldehydes was reported by Geetharani and Bose in 201825. Expanding beyond ketones, there has been more exploration into utilizing CO with iron catalysts. Bontemps and Sabo-Etienne demonstrated that Fe(H) (dmpe) could hydroborate CO with various borane agents, leading to the formation of methoxyboranes or bis(boryl)acetals46. Moreover, Bontemps combined Fe-catalyzed bis(boryl)acetal production with organic and chemoenzymatic catalysis in a one-pot reaction, achieving enantioselective transformation of CO into carbohydrates47.

Cantat and Berthet reported an iron complex supported by a tripodal phosphine ligand PhSi(XPPh ) , where (X=CH , O) for the reduction of CO to methoxyborane with 9-Borabicyclo[3.3.1]nonane dimer(9-BBN) at 60°C48. Webster contributed to the field by utilizing an air-stable [Fe(salen)] -μ-oxopre-catalyst with HBpin for the reduction of ketones, aldehydes, and CO 49 More recently, Wang and co-workers have demonstrated cooperative catalysis with Cp*Fe(Cy PN=CH N), showcasing sequential CO hydroboration and N-formylation50. To the best of our knowledge, at the time of print, there has been no reported iron-catalyzed double hydroboration of cyclic esters.

Results
We have previously demonstrated that a diphosphinoborane-iron complex (complex A, Fig. 1) is efficient for the catalytic hydroboration of olefins51. Building upon these findings, we sought to expand the catalytic capabilities of A by exploring its potential in C–O multiple bond reductions, including ketones, cyclic esters, and CO , using HBpin, and in the case of CO , (9-BBN) . Additionally, we aimed to gather kinetic information on the hydroboration of ketones to gain insights into the catalytic cycle.

To begin our study, we examined whether A would be an efficient pre-catalyst for hydroboration of ketones. We conducted a series of optimization reactions, using our model substrate, cyclohexylphenyl ketone and the economical reductant, HBpin (see ESI for optimization table). A preference for non-coordinating aryl solvents was observed, namely benzene and toluene, with benzene returning a slightly higher yield. Under optimized conditions, the reaction proceeded at ambient temperature with 1 mol% catalyst loading of A, resulting in an excellent isolated product yield within 5 h (99%). We employed a control reaction with catalyst-free conditions, after 96 h at ambient temperature, the isolated boronic ester was obtained in a significantly lower yield of 23%.

With the optimal conditions in hand, we turned our attention to exploring the scope of ketones (Fig. 2). Simple aromatic ketones such as acetophenone (2a) and its derivatives all underwent clean conversion in less than 10 min, exhibiting a resilience to electron-donating/-withdrawing substituents and steric bulk around the aromatic ring on the phenyl ring (2b–e). Ketones bearing cyclobutyl or thiophene groups (2f and 2g, respectively) were also successfully hydroborated in less than 10 min with >95% isolated yield. When the steric bulk of the aliphatic group was increased from a methyl to a tert-butyl (2h) or cyclohexyl (2i) group, increased reaction times were required, with a moderate decrease in yield for 2h also being observed. The limitation of steric bulk on the performance of pre-catalyst A became evident in 2m, where, after 24 h at ambient temperature, the hydroborated product was achieved in a moderate 61% yield, while the less encumbered 2l was obtained in 91% yield after 30 min. This discrepancy suggests that the added methyl groups on 2m are enough to hinder the transfer of the hydride. As we have previously reported, complex A cannot tolerate simple halogen substituents (Cl, Br and I), with the exception of fluorine, due to irreversible degradation of the iron center52. Furthermore, hydroboration of a pyridine-containing ketone 2k resulted in the selective reduction of the ketone without any observed reduction of the pyridine moiety. Notably, when cyclohexen-2-one was used as a substrate, complete 1,2-selectivity was observed (2n) with the olefin moiety remaining intact after 24 h.

With these encouraging results, we extended our investigation to other C=O-containing systems. Based on the exquisite chemoselectivity observed in product 2r, we wondered if ester-containing substrates such as methyl benzoate derivatives could be reduced; however, even with high catalyst loading (20 mol%) and elevated temperatures (110°C), this was not possible with only starting material being recovered. This selectivity can be attributed to the lower Lewis basicity of esters, precluding the formation of a catalytically active species, as observed by 1H NMR spectroscopy (see Supporting Information). We therefore shifted our attention to the more reactive, conformationally locked cyclic esters, which readily underwent double hydroboration with 5 mol% catalyst loading and 2.1 equivalents of HBpin under mild conditions (Fig. 2b). A variety of ring sizes were investigated (n=5, 6 and 7) with γ-butyrolactone, δ-valerolactone and ε-caprolactone all undergoing smooth reduction to afford the corresponding borylated diols (4a, 4b and 4c, respectively) in excellent yields. Reduction of phthalide and 3-isochromanone was also achievable, albeit at a higher temperature (50°C) and longer reaction times.

Finally, we directed our focus to the hydroboration of carbon dioxide. Hydroboration proceeded in a J. Youngs NMR tube loaded with HBpin, 1 atm dry CO and 2.5 mol% of A in C D (0.6 ml); the reaction was monitored by 1H and 11B NMR spectroscopy, with partial consumption of HBpin at ambient temperature within 6 h being observed. Analysis of the 1H NMR spectroscopic data revealed the formation of Bpin derivatives of formoxy (5), acetal (6) and methanol (7), Table 1. Using hexamethylbenzene as an internal standard to calculate solution yield, we observe a very slight selectivity towards 6 and 7, both yielding 14%, closely followed by 5 with 10% conversation. In 11B NMR spectroscopy, we also observe the presence of O(BR) . Due to the only modest conversion of HBpin and no clear selectivity to one product an alternative borane source, (9-BBN) was screened under the same conditions described. Using (9-BBN) with no catalyst led to no observable reduction products by 1H NMR spectroscopy, even after extended reaction times (72 h); however, when the reaction was repeated with 2.5 mol% of A, full consumption of the borane is observed using 11B NMR spectroscopy within 15 min. From the 1H NMR spectroscopic data, adduct 7 was exclusively observed in 66% yield. Encouraged by these results, we explored the possibility of reducing the catalyst loading of A to 1 mol%. At ambient temperature, (9-BBN) was consumed within 1 h, leading to product distribution comparable with the higher catalyst loading, yielding 65% of 7 with some O(BR ) observed by 11B NMR spectroscopy. To confirm results, each experiment was repeated, giving comparable results as seen in the supporting information.

Kinetic Studies
To further ascertain mechanistic insights into the hydroboration of ketones, a kinetic investigation was undertaken. Cyclohexylphenyl ketone was selected as the representative substrate due to its slower reaction rates. Initial reactions were monitored by 1H NMR spectroscopy following the growth of the hydroboration product, 2i at 273 K using the standard reaction conditions of 1 mol% complex A and a 1:1.1 ratio of ketone (0.313 M) to HBpin (0.344 M), (Fig. 3). A fractional dependence on [A] is deduced through the variation of the catalyst loading whilst keeping the concentrations of ketone and HBpin constant (Fig. 3a). This dependency is suggestive of a dissociative process where one equivalent of an ‘active’ and one equivalent of an ‘inactive’ monomer is generated, as observed by the linear dependency of K obs vs [A] (see supporting information). This slightly higher than half-order dependency can be attributed to an equilibrium process where the inactive monomer dissociates an N moiety and can then engage in catalysis. Variation of the [ketone] revealed a major dependence on the reaction stoichiometry with maximum saturation in ketone concentration limits reminiscent of enzymatic kinetics (Fig. 3b). This plateauing of the reaction rate at high ketone concentrations could be attributed to the competing formation of an off-cycle ketone-iron complex. Unfortunately, attempts to isolate or identify this putative species proved unsuccessful. At low concentrations of ketone, a pseudo-first-order dependency is observed, suggestive of its participation in the rate-determining step prior to potential catalyst saturation. Finally, the order in [HBpin] was determined by variation of the [HBpin] under standard reaction conditions and indicated an inverse order law order in [HBpin]; d Initial rates of ketone hydroboration with HBpin and DBpin for KIE determination. To elucidate the nature of this inverse order in HBpin, we explored the reaction of HBpin with both the ketone and complex A. Notably, 1H and 11B NMR spectroscopy provided no evidence for a ketone-HBpin adduct nor an adduct of complex A-HBpin. These data indicate a more complex process is in operation other than a two-component assembly and are suggestive of a three-component assembly between the iron, ketone and HBpin in the rate-determining step. Interestingly, a strong dependence on the order of substrate addition was observed. For the substrate scope and kinetic experiments, the ketone and A were pre-mixed, followed by the addition of HBpin. We observed that when the ketone and HBpin are pre-mixed prior to the addition of A, there is a considerable decrease in the rate from 7.1 × 10−5 to 2.72 × 10−5 M/s, respectively. This reinforces the inverse order dependency observed for HBpin, implying a competitive inhibition reaction preventing the formation of the active catalyst.

A comparison of the pseudo-first order rate constants for hydroboration of cyclohexylphenyl ketone in which HBpin was exchanged for DBpin provided a kinetic isotope effect (KIE, k /k ) of 2.21 (Fig. 3d). Although considered a relatively small KIE value, this constitutes a large secondary kinetic isotope effect and is comparable to results (k /k =1.62) reported by Hill et al., during studies of magnesium-catalyzed hydroboration, in which B–H bond cleavage is part of the rate-determining step52.

Stoichiometric Studies
To gain insight into these catalytic reactions, a series of stoichiometric reactions were conducted. Monitoring of NMR-scale reactions performed using cyclohexylphenyl ketone was particularly informative. We previously reported that A reacts with an excess of HBpin to generate an iron(II) dihydride species (B), along with B pin and PhBpin within 6 h at 50°C, with no reaction observed at room temperature53. When B was reacted with an equimolar quantity of cyclohexylphenyl ketone, no reaction was observed at room temperature after 16 h. These results provoked a more in-depth investigation into how A interacts with substrates. We were particularly interested in how the carbonyl motif of the ketone may coordinate to the iron center (i.e., η1-through the oxygen or η2 through the π-bond, as reported for the analogous Ni-complex)53.

A reaction using an equimolar quantity of cyclohexylphenyl ketone resulted in partial consumption of A to generate a new paramagnetic species, evidenced by 1H NMR spectroscopy; however, only a small amount was converted and was not stable to isolation. Even in catalytic equivalents, complete conversion of complex A into a new species is not observed, which could be attributed to the half-order dependency observed in kinetic analysis. When ketones bearing aromatic substituents were mixed with complex A, a color change from red to purple occurred and new paramagnetic species were observed by 1H NMR spectroscopy; however, these quickly decomposed upon isolation. Addition of benzophenone to complex A in C D also resulted in an immediate color change from dark red to intense purple. 1H NMR spectroscopy showed full conversion of A with 15 new paramagnetically shifted resonances, indicating C symmetry in solution. An iron-ketyl radical complex, [(iPrDPBPh)Fe(OC(Ph) )](9), was isolated, and crystals suitable for X-ray crystallographic studies were grown from slow evaporation of diethyl ether (Fig. 4a). The benzophenone is coordinated to the iron center exclusively via the oxygen, resulting in a pseudo-tetrahedral iron center (τ =0.71). Upon analysis of bond metrics, an elongation of the C–O bond length (1.295(3)Å) in comparison to the free benzophenone C=O bond length (1.2233(17)Å) was observed. This bond length is comparable to that observed for an authenticated neutral iron(II)-benzophenone ketyl radical (1.2989(19)Å) reported by Gade54. Equally, the Fe–O bond length of 1.8364(18)Å is similar to the only other reported iron-ketyl complexes by Gade54 and Werncke55 (Fe(II)–O 1.8565(10)Å and 1.869(1)Å) and is in good accordance with an Fe(I) species bearing an anionic oxygen donor ligand56.

UV-Vis spectroscopic analysis of 9 showed two distinct absorptions at 522 nm and 652 nm, which is consistent with previously reported benzophenone ketyl radicals (Fig. 4b)55,56. From TD-DFT calculations, the absorption at 522 nm is attributed to the π(ketyl) to π*(borane) transitions (computed as 490 nm), whereas the absorption at 652 nm (TDDFT value of 605 nm) is attributed to the π(ketyl) to π*(borane) and π(ketyl) to π*(ketyl) transitions, which both share considerable ligand to metal charge-transfer (LMCT) character (see supporting information). X-band EPR-spectroscopy was performed at 5 K in toluene glass to try and observe a g-value around 2.00, indicative of the presence of the organic ketyl radical. No such absorptions were observed, suggesting complex 9 has an overall whole integer spin.

To rationalize the absence of the g=2.00 EPR absorption and gain further insight into the electronic structure of 9, their magnetic properties in both solution (Evans method) and the solid state were probed. The effective magnetic moment (μ =2.76 μ ) in solution is in good agreement with the value obtained in the solid state at 300 K (μ =3.12 μ ). The magnetic data are consistent with what would be expected for an S=1 system. The χ T vs. T slope depicts a steady decrease to 50 K followed by a sharp drop from 50 K to 2 K (Fig. 4c). Interestingly, the χ T vs. T curve does not plateau at higher temperatures suggesting the presence of antiferromagnetic coupling between an unpaired electron on the iron and the ketyl radical. To understand how we obtain an S=1 system with antiferromagnetic coupling, DFT calculations were performed using both the ωB97X-D3 and CAM-B3LYP levels of theory, along with the def2-SVP basis set. SCF stability calculations consistently show a broken spin-symmetry solution, corresponding to four unpaired electrons, with antiferromagnetic coupling. The resulting spin density is shown in Fig. 4d. A Natural Bond Orbital (NBO) analysis reveals three unpaired electrons on the Fe center delocalized across the d xy , d xz , d x2(cid:1)y2 and d z2 orbitals, with antiferromagnetic coupling to the unpaired electron on the ketyl radical moiety. Calculated values of the approximate antiferromagnetic coupling gave a value of −2071 cm−1, qualitatively indicating strong antiferromagnetic coupling between the ketyl and Fe sites.

To ascertain if the iron(I)-ketyl radicals are part of the on-cycle pathway, complex 9 was subjected to 10 equivalents of HBpin under standard reaction conditions and monitored by 1H NMR spectroscopy. After 25 min, only a trace amount of hydroborated product 2j was observed. After 16 h, complete conversion of complex 9 to 2j and complex A was observed, suggesting the ketyl-radical is in equilibrium with the carbonyl-bound species. To further probe the possibility of a radical pathway, inhibition experiments were conducted using the radical scavenger styrene and the radical inhibitor BHT under standard conditions. No decrease in the yield of 2j was observed in both cases, suggesting that a radical pathway is not in operation. To further probe the involvement of radicals in this transformation, a radical clock experiment was conducted. Radical ring-opening products were not observed, whilst the hydroborated product 2p was isolated in 94% yield, further suggesting a two-electron pathway is in operation (Fig. 5).

DFT studies
Dimeric pre-catalyst complex A initially coordinates HBpin, before the dimer splits into 11 (with HBpin) and 12 (with N bound). The ketone (2i) then forms a B–O bond with the bound Bpin, before a Fe-mediated ligand to ligand hydride transfer (LLHT), before elimination of the hydroborated product to reform A, which re-enters the catalytic cycle. Following the formation of the B–O bond, the rate-limiting step is the hydride transfer (Fig. 6, ‡11–13 (2)), supported by the KIE data presented earlier. The barrier is ~5 kcal mol−1 lower in energy than the equivalent transition state for HBpin and the ketone reacting together in the absence of A. At the transition state of 11–13, the out-of-plane B–H bond is responsible for the higher reactivity, forming the new B–C bond, while coordination to the Fe complex reduces the energy barrier for the hydride transfer. Coordination of 12 to this complex appears to be essential in reducing this barrier and supports the hypothesis from the kinetic data that only a fractional quantity of the Fe centers in A are involved in the catalytic step; the transition state is >5 kcal mol−1 higher without 12 present. The energies of the different minima with different spin multiplicities are given in Table S3.

Alternative pathways were considered, where in all cases the hydride transfer step was significantly higher than the LLHT barrier height (Fig. S10 in the Supporting Information). In the alternative to the LLHT step, the (rate-limiting) barrier height was calculated to be 29.1 kcal mol−1, while in the pathway in which the ketone coordinates to the Fe complex first, the rate-limiting barrier height is 31.6 kcal mol−1 (top in the alternative pathway, Fig. S10) and 38.2 kcal mol−1 (bottom in the alternative pathway, Fig. S10). Based on the kinetic data obtained, DFT results, and previous mechanistic studies conducted using iron-diphosphinoborane complexes, a plausible catalytic cycle can be tentatively assigned for cyclohexylphenyl ketone (Fig. 7)51,53,56,57.

In summary, complex A has been demonstrated as an active pre-catalyst for hydroboration of a broad range of ketones, cyclic esters, and CO to form boryl ethers under mild conditions. The hydrofunctionalization of CO by (9-BBN) led to the selective formation of methoxy borane in less than 1 h at ambient temperature. Stoichiometric reactions have shown that in the case of sterically unhindered ketones, the substrate coordinates to the iron center with a loss of N , and this is believed to be the entry point in the catalysis. Kinetic studies with cyclohexylphenyl ketone demonstrated an inverse dependency for HBpin and a KIE value of 2.21, indicating that B–H cleavage is likely the rate-determining step. From DFT studies, the hydride transfer step proceeds via direct LLHT, which is mediated by the iron. An unreported iron(I)-ketyl radical was isolated from the reaction of A with benzophenone, with magnetic measurements and DFT studies revealing an S=1 iron center containing three unpaired electrons on iron and an antiferromagnetically coupled ketyl radical.

Methods
Provided here are key protocols
Complete experimental details (general considerations, synthesis & characterization data, catalytic reactions, reactivity studies, kinetics measurements) and further computational details are provided in the Supplementary Information.

Synthesis of [{(iPrDPBPh)Fe} 2 (µ-1,2-N 2 )](Complex A)
The iPrDPBPh ligand (1.33 g, 2.81 mmol) and FeBr (0.602 g, 2.81 mmol) were stirred at R.T. in THF (80 mL) until all solids dissolved into a yellow solution. Volatiles were removed in vacuo, generating yellow/orange solids, this was left under a vacuum for 30 min after all solvents were visibly removed. Et O (100 mL) was added to the solids and stirred vigorously for 1 h to produce a bright yellow precipitate, volatiles were removed in vacuo and the remaining solids were subsequently dissolved in benzene (100 mL) and allowed to stir overnight before being added to a 1% Na/Hg amalgam (Na: 291 mg, 0.013 mol) and left to stir for 16 h at R.T. The dark red solution was filtered through Celite® and volatiles were removed in vacuo. Dark brown/red solids were washed in pentane (20 mL), solids were dried in vacuo before being washed in cold Et O (2×10 mL) (0.974 g, 1.83 mmol, 65%). 1H NMR (400 MHz, C D ) δ 135.00, 44.52, 34.77, 28.38, 26.50, 7.46, 0.32, –1.45, –2.28, –6.25, –9.23, –76.98 ppm.

Synthesis of [(iPrDPBPh)Fe(OC(Ph) 2 )](9)
Complex 9 was prepared by dissolving complex A (82 mg, 0.150 mmol) and benzophenone (27.2 mg, 0.150 mmol) in C D (0.6 ml). Immediately, the color changed from dark red to dark purple at R.T., volatiles were removed in vacuo, affording 9 as a dark solid. Slow evaporation from a concentrated solution of diethyl ether gave dark purple single crystals suitable for XRD (101 mg, 0.141 mmol, 94%). 1H NMR (400 MHz, C D ) δ 132.20, 126.21, 48.60, 37.76, 35.20, 22.83, 4.96, 2.41, 0.02, –3.78, –5.77, –8.79, –14.25, –29.77, –31.28. ATR-IR (cm–1) 1359 (C–O). Solution magnetic moment (25°C, C D ) 2.76 μB. UV-vis [toluene, λ(nm){ε(M-1cm–1)}]: 522 (8345), 622 (6376).

General procedure 1: hydroboration of ketones
In a nitrogen-filled glove box, an oven-dried J-Youngs NMR tube was charged with [{(iPrDPBPh)Fe} (μ-1,2-N )] (0.00206 mmol), C D (0.6 mL), substrate (0.205 mmol), HBpin (0.225 mmol), followed by toluene (0.205 mmol) as an internal standard for NMR quantification. The reaction mixture was left at R.T. until reaction was complete (0.1–24 h), monitored by 1H NMR spectroscopy. Volatiles were removed in vacuo, the mixture was suspended in Et O and filtered through a short plug of Celite® in a glove box, and volatiles were removed in vacuo to reveal the isolated product.

General procedure 2: hydroboration of cyclic esters
In a nitrogen-filled glove box, an oven-dried J-Youngs NMR tube was charged with [{(iPrDPBPh)Fe} (μ-1,2-N )] (0.005 mmol), C D (0.6 mL), substrate (0.103 mmol), HBpin (0.225 mmol), followed by toluene (0.103 mmol) as an internal standard for NMR quantification. The reaction mixture was either left at R.T. or added to an oil bath (50°C) for 4–48 h and monitored by 1H NMR spectroscopy. Volatiles were removed in vacuo, the mixture was suspended in Et O and filtered through a short plug of Celite® in a glove box, and volatiles were removed in vacuo to reveal the isolated product.

General procedure 3: hydroboration of carbon dioxide
In a nitrogen-filled glove box, the desired amount of [{(iPrDPBPh)Fe} (μ-1,2-N )] 2.5 mol% – 1 mol% was dissolved in 0.6 mL of C D with HBR (0.205 mmol) and hexamethylbenzene as an internal standard for NMR quantification in a J-Youngs NMR tube. The NMR tube was taken out of the glove box and degassed by freeze-pump-thaw, then back-filled with CO (1 bar) from a cylinder. Yields were calculated by 1H NMR spectroscopy.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The work by Willcox and Robinson describes the use of an iron(0) metalloborane complex as a precatalyst for hydroboration of ketones, cyclic esters and CO2 under mild conditions. Mechanistic investigations, including DFT calculations, suggest that ketone hydroboration likely proceeds via an Fe-mediated ligand-to-ligand hydride transfer (LLHT) mechanism. Notably, the authors have isolated an off-cycle iron(I)-benzophenone ketyl radical complex with an S = 1 antiferromagnetic ground state, offering valuable mechanistic insights. Although the hydroboration of carbonyls has been extensively studied, the authors claim an \"unprecedented Fe-mediated LLHT mechanism\"; however, LLHT pathways are actually quite common in metal-catalyzed hydroboration reactions.\nMy primary concern is a mechanistic inconsistency: the authors report that complex A does not react directly with HBpin at room temperature but does activate benzophenone to generate the ketyl radical. Nevertheless, the mechanism proposed in Figure 2 depends on HBpin activation, which appears contradictory.\nIn my opinion, the most novel aspect of this work is the direct activation of benzophenone to form the iron(I)-benzophenone ketyl radical, with significant implications for catalytic transformations. While this study is interesting and potentially suitable for publication in Nature Communications, further experimental and computational studies are needed to clarify the initiation step—specifically, whether catalysis is triggered by substrate activation or HBpin activation.\nMore scientific considerations:\n1.The claim of an \"unprecedented Fe-mediated LLHT mechanism\" should be tempered, as Fe–H transfer to a carbonyl carbon is a well-known process in transition metal-catalyzed hydroboration.\n2.The Figure 1 caption refers to a \"van’t Hoff plot,\" but the data illustrate k_obs versus substrate/catalyst concentration. Please correct this mislabeling.\n3.For CO₂ hydroboration, control experiments with (9-BBN)₂ should be provided to establish baseline reactivity.\n4.The stated \"1:1 ratio of ketone (0.313 M) to HBpin (0.344 M)\" is inaccurate and should be clarified or corrected.\n5.The explanation, \"At low ketone concentrations a pseudo first-order dependency is observed suggesting that the ketone is required up to and including the rate-determining step,\" is confusing and should be revised for clarity.\n6.Please address whether complex A (Fe(0)) could undergo oxidative addition with HBpin to form Fe–H/Fe–Bpin, with Fe–H as the active catalyst. Alternatively, is cooperative H–B activation by Fe–B in intermediate 11 via a four-membered transition state feasible for hydride/Bpin transfer to the carbonyl?\n7.In Scheme 4, correct the labeling of intermediates 11 and 12 from \"PH\". Also, ensure that panels a, b, c, d in Figure 1 are properly labeled, and check the designation for compound 2i.\n8.The mechanistic section is difficult to follow; additional calculations and clarification are needed regarding the initiation step.\n9.For the monomeric Fe(I) species in Figure 3, did the DFT calculations consider all relevant spin states (doublet, quartet, sextet)? Please report the relative energies in the Supporting Information.\n10. What is the activation barrier for the background (uncatalyzed) process?\n11.In the proposed rate-limiting transition state, the metal appears to have weak interactions with the substrates. Is this plausible? The computed barrier of 26.2 kcal/mol suggests the reaction may not occur at room temperature.\n12.All optimized coordinates should be included in the Supporting Information.", "reviewer_2": "The manuscript by Willcox, Robinson and coworkers reports on an iron metalloborane dinitrogen complex that catalyzed the hydroboration of ketones, cyclic esters and carbon dioxide. This is a nice piece of work that represents a detailed study on earth-abundant iron-catalyzed reactions with a range of carbonyl substrates. Both experimental and computational work has been conducted for uncovering the mechanistic aspect, along with the isolation and characterization of a novel iron-ketyl radical complex resulting from the stoichiometric reactions. While this reviewer is mostly positive on the overall quality of the work, the following factors diminish my enthusiasm about its publication in this high impact interdisciplinary journal. A more specialized journal in catalysis would be better suited.\n1, both the catalyst and the catalytic reactions presented here are not new and in fact the hydroboration of carbonyl compounds has been long explored with numerous catalysts or even without a catalyst in the literature. The mechanistic study is much appreciated, yet it does not represent any conceptual advances that justify a publication in Nature Communications. The isolation of an iron-ketyl radical product was significant, but turned out not to be a key intermediate in the catalytic cycle. Thus, it did not benefit the mechanistic understanding.\n2, as for the catalytic reactions, the substrate scope was not well studied. More challenging substrates containing reducible functional groups should be included. It was also unfortunate to display poor catalytic activity towards general ester substrates.", "reviewer_3": "The article by Grose et al. describes an experimental and computational study into very interesting iron boron chemistry for hydroboration of carbonyl containing compounds, and they describe the isolation of a unique iron(I) ketyl complex in an antiferromagnetic ground state. The manuscript is well written and the topic is of high scientific interest.\nOverall the work is highly interesting both in terms of experiment and theory.\nI will focus my review on the computational work in this study and I ask the authors to consider the comments below:\n1) In iron coordination compounds, the electronic structure may have a large flexibility in spin states depending on the detailed surroundings. This is apparent in the intricate electronic structure found for antiferromagnetically coupled complex 9, but it will also play a role in the dinuclear N2-bridged complex A. Assuming S=1 for the two Fe centres, it is not obvious how the magnetic moments of the two iron centres are coupled and what the electronic ground-state structure looks like. Further, in terms of reaction kinetics and thermodynamics the concept of two-state or multi-state reactivity involving spin crossover steps is often relevant. Therefore the electronic structure of all Fe containing species must be carefully evaluated in order to ascertain the ground-state potential energy surface.\n2) With regard to reactivity the entropic contributions cannot be neglected in my opinion. This is particularly true for reaction steps involving the cleavage/formation of dimeric structures or, in general, steps involving change in particle numbers.\n3) I would be interested to learn more about the authors’ perspective on why the iron ketyl radical 9 exhibits such unusual antiferromagnetic features. Are there particular properties of the iron-boron interaction and/or the iron-carbonyl bond that govern the antiferromagnetic ground state? Or conversely, what inhibits this antiferromagnetic behaviour in other iron-ketyl compounds? Further elaboration would enhance the impact of the manuscript.\nFurther specific remarks\nMain text:\nComputational study of 9:\nHow does the computed molecular structure/geometry compare with that extracted from XRD?\nPlease report the relative energies of the neighbouring (pure) spin multiplicities, S=2 quintet and S=0 closed-shell singlet.\nPlease state the isodensity value for the spin density plot in Figure 2d.\nPlease state the <S**2> value for 9 also somewhere in the main text (e.g. in the caption of Figure 2d).\nThe spin populations (NPA or Mulliken) on the relevant atomic sites (Fe, B, Fe-coordinated phenyl, O, rest of the ketyl group) should be reported - in the ESI as appropriate.\nEnergy profile for hydroboration:\nIt is not clear which energy values are reported for the computed potential energy surface:\nOn the y-axis of Figure 3 \"Delta-H + ZPE\" is given. This is a conflicting description. Delta-H would already include ZPE.\nPerhaps \"Delta-E + ZPE\" is meant? Then these values would correspond to zero K data. Is this the case here?\nPlease report Gibbs energies including entropy contributions at r.t. instead of just enthalpies (or energies at zero K). This is particularly important for comparison with experiment and for assessment whether a barrier height is rate limiting or not.\nIf I understand correctly, only the S=1 triplet spin surface is considered. Other spin multiplicities might play a role here, and these should be investigated and discussed in the same detail (or excluded if applicable).\nSupporting information:\nPlease report the corresponding transition wavelengths/energies of the TD-DFT results. How does the computed spectrum compare to the experimentally observed one?\nFigures S8-S10:\nIt is not clear which spin surface the PES refers to. Please report specifics on the electronic structure, at least the spin multiplicity of the species in the PES.\nFor comparison with experiment, Gibbs free energies at r.t. should be reported instead of \"enthalpies plus ZPE\".\nThe electronic structure of species A should be discussed in a little detail:\n- How are the two magnetic iron centres coupled?\n- Why are other spin multiplicities not considered or discussed?\n- How is the possibility of spin change across the PES excluded?\nPlease carefully check and amend the References in the ESI.\nHere are two examples:\nReference 13 seems incomplete.\nThe authors' list in Reference 15 for the QChem package doesn't look right.\nPlease include Cartesian coordinates, total energies and spin expectation values for all computed species."}, "author_response": "We thank all the reviewers for their comments and our responses to the rebuttals below are in purple.\nThe appropriate changes have been made to the manuscript and SI and are identifiable as track changes\nthroughout the documents.\nReviewer #1 (Remarks to the Author):\nThe work by Willcox and Robinson describes the use of an iron(0) metalloborane complex as a\nprecatalyst for hydroboration of ketones, cyclic esters and CO2 under mild conditions. Mechanistic\ninvestigations, including DFT calculations, suggest that ketone hydroboration likely proceeds via an\nFe-mediated ligand-to-ligand hydride transfer (LLHT) mechanism. Notably, the authors have isolated\nan off-cycle iron(I)-benzophenone ketyl radical complex with an S = 1 antiferromagnetic ground\nstate, offering valuable mechanistic insights. Although the hydroboration of carbonyls has been\nextensively studied, the authors claim an \"unprecedented Fe-mediated LLHT mechanism\"; however,\nLLHT pathways are actually quite common in metal-catalyzed hydroboration reactions.\nDuring the preparation of this manuscript, a detailed literature search revealed that there were no\ndirect LLHT processes catalyzed by transition-metal complexes for carbonyl hydroboration, however,\nLLHT has been reported for s-block catalysts (ACS Omega, 2019, 4, 15893–15903). LLHT has been\nreported for Fe-catalyzed hydrosilylation of alkynes, however, this is reported to proceed via the\nformation of a discrete Fe(II) Fe-H/Fe-Si species (J. Am. Chem. Soc. 2020, 142, 16894–16902).\nMy primary concern is a mechanistic inconsistency: the authors report that complex A does not react\ndirectly with HBpin at room temperature but does activate benzophenone to generate the ketyl radical.\nNevertheless, the mechanism proposed in Figure 2 depends on HBpin activation, which appears\ncontradictory.\nWe thank the reviewer for pointing this out. We agree that the way we had drawn the proposed\nmechanism and the structures in the DFT calculated pathway are ambiguous, causing much of the\nconfusion noted by reviewers below. During the DFT studies, the direct activation of HBpin by\ncomplex A was much higher in energy compared to the formation of the sigma-complex. We\nrepresented this sigma-complex as a 3-memebered ring which could look like activation of the H–B\nbond. In the revised figure and scheme, this sigma-complex has been represented by a bond from the\niron to the centre of the B–H bond to overcome this potential issue.\nIn my opinion, the most novel aspect of this work is the direct activation of benzophenone to form the\niron(I)-benzophenone ketyl radical, with significant implications for catalytic transformations. While\nthis study is interesting and potentially suitable for publication in Nature Communications, further\nexperimental and computational studies are needed to clarify the initiation step—specifically, whether\ncatalysis is triggered by substrate activation or HBpin activation.\nFrom an experimental stand, no activation of the B–H bond is observed when HBpin is reacted with\ncomplex A at room temperature. Regarding the substrate activation, we see no formation of an Fe-\nKetone species via 1H NMR spectroscopy, with only complex A and the ketone resonances\nobservable. This is also supported by a Job’s plot type analysis where a flat line was observed\nmeaning there is no complex formation between Fe and the ketone – presumably due to the steric bulk\nof the ketone, which is represented by the prolonged reaction time for this substrate. From the DFT\ncalculations and the Job plot type analysis, a three-component transition state is required for the\ncatalysis to occur, rather than specific activation of either the borane or the ketone.\nMore scientific considerations:\n1.The claim of an \"unprecedented Fe-mediated LLHT mechanism\" should be tempered, as Fe–H\ntransfer to a carbonyl carbon is a well-known process in transition metal-catalyzed hydroboration.\nWhilst the formation of an Fe–H might be well-precedented in hydroboration chemistry (and we have\npreviously reported this activation pathway for olefin and nitrile reduction), this reduction process\ntransfers the H from HBpin directly to the ketone without the formation of a discrete Fe–H complex.\n2.The Figure 1 caption refers to a \"van’t Hoff plot,\" but the data illustrate k_obs versus\nsubstrate/catalyst concentration. Please correct this mislabeling.\nThis has been changed in the manuscript.\n3.For CO₂ hydroboration, control experiments with (9-BBN)₂ should be provided to establish baseline\nreactivity.\nThis has been added to the manuscript (Table 1 entry 2, Page 4)\n4.The stated \"1:1 ratio of ketone (0.313 M) to HBpin (0.344 M)\" is inaccurate and should be clarified\nor corrected.\nThis has been corrected to 1:1.1\n5.The explanation, \"At low ketone concentrations a pseudo first-order dependency is observed\nsuggesting that the ketone is required up to and including the rate-determining step,\" is confusing and\nshould be revised for clarity.\nWe have revised this statement in the manuscript and replaced it with “At low concentrations of\nketone, a pseudo first-order dependency is observed suggestive of its participation in the rate-\ndetermining step prior to potential catalyst saturation.”\n6.Please address whether complex A (Fe(0)) could undergo oxidative addition with HBpin to form\nFe–H/Fe–Bpin, with Fe–H as the active catalyst. Alternatively, is cooperative H–B activation by Fe–B\nin intermediate 11 via a four-membered transition state feasible for hydride/Bpin transfer to the\ncarbonyl?\nFrom an experimental perspective, no direct oxidative addition of HBpin via complex A is observed\nby 1H or 11B NMR spectroscopy. In a previous study, we did observe the formation of an Fe-H/Fe-\nBpin species (Chem Commun, 2023, 59, 7427), however this is only generated at elevated\ntemperatures and when this species was subjected to a stoichiometric quantity of ketone, no reduction\nproducts were observed. From the computational calculations, the barriers to formation of 10a from\n10 (activation of B-H bond on one Fe centre) and then from 10a to 11 (breakup of the dimer “A”) are\n11.1 and 11.6 kcal mol-1, respectively. This step seems to be key to breakup of the dimer. Direct\nactivation of B-H by either monomer of A is 24.1 kcal mol-1 (with barrier to hydride transfer in excess\nof 30 kcal mol-1). The cooperative transition state was extensively searched for but consistently\nresulted in the 10a structure we have presented, despite attempting many different starting geometries.\n7.In Scheme 4, correct the labeling of intermediates 11 and 12 from \"PH\". Also, ensure that panels a,\nb, c, d in Figure 1 are properly labeled, and check the designation for compound 2i.\nWe thank the reviewer for highlighting this. This has now been addressed in the manuscript.\n8.The mechanistic section is difficult to follow; additional calculations and clarification are needed\nregarding the initiation step.\nWe have re-written the kinetics study section and made the order in Fe and ketone easier to follow\nwith a more detailed interpretation of the results. Both experimental and computational results\nindicate initiation is not due to B-H activation, but requires a three-component transition state (as\ndiscussed in the answer to the comment “…further experimental and computational studies are needed\nto clarify the initiation step…” above. Additionally, our changes to the proposed catalytic cycle figure\n(Scheme 4, page 9) make this section fully consistent (as discussed above in our response to the\ncomment: “My primary concern is a mechanistic inconsistency…”).\n9.For the monomeric Fe(I) species in Figure 3, did the DFT calculations consider all relevant spin\nstates (doublet, quartet, sextet)? Please report the relative energies in the Supporting Information.\nThe energies for the different spin states are: Quintet -3713.6985053877, Triplet -3713.7770516369.\nThese are presented in the supporting information (note that the complex was neutral overall).\n11.In the proposed rate-limiting transition state, the metal appears to have weak interactions with the\nsubstrates. Is this plausible? The computed barrier of 26.2 kcal/mol suggests the reaction may not\noccur at room temperature.\nThe calculated barrier is 24.2 kcal/mol with respect to the reactants, which is feasible (using the\nEyring equation predicts a half-life of ~17 hours, which is in line with the experimental data, if\nslightly longer). All other “rate-limiting” transition states for the different pathways were considerably\nhigher in energy, usually > 30 kcal/mol.\n12.All optimized coordinates should be included in the Supporting Information.\nWe apologise for mistakenly omitting these, they are now included in the revised submission.\nReviewer #2 (Remarks to the Author):\nThe manuscript by Willcox, Robinson and coworkers reports on an iron metalloborane dinitrogen\ncomplex that catalyzed the hydroboration of ketones, cyclic esters and carbon dioxide. This is a nice\npiece of work that represents a detailed study on earth-abundant iron-catalyzed reactions with a range\nof carbonyl substrates. Both experimental and computational work has been conducted for uncovering\nthe mechanistic aspect, along with the isolation and characterization of a novel iron-\nradical complex resulting from the stoichiometric reactions. While this reviewer is mostly positive on\nthe overall quality of the work, the following factors diminish my enthusiasm about its publication in\nthis high impact interdisciplinary journal. A more specialized journal in catalysis would be better\nsuited.1, both the catalyst and the catalytic reactions presented here are not new and in fact the\nhydroboration of carbonyl compounds has been long explored with numerous catalysts or even\nwithout a catalyst in the literature. The mechanistic study is much appreciated, yet it does not\nrepresent any conceptual advances that justify a publication in Nature Communications. The isolation\nof an iron-ketyl radical product was significant, but turned out not to be a key intermediate in the\ncatalytic cycle. Thus, it did not benefit the mechanistic understanding.\nWe thank the reviewer for their comments. We are not suggesting that the catalyst nor the transformation\nitself are new, but that this class of Fe(0) complexes have rarely been screened in catalysis and therefore,\noffers a unique possibility to explore how these complexes behave. The mechanistic evidence\n(experimental and computational) supports a mechanism which hasn’t been previously reported for\ntransition metal complexes and is different to the mechanism we report in our previous study which\nproceeds via an Fe–H/Fe–Bpin species (Chem. Eur. J, 2025, 31, e202501782) rather than a direct Fe(0)-\nmediated LLHT. Whilst the Fe(I)-ketyl species is off-cycle, this represents the first example of an Fe(I)-\nketyl complex which could have further implications for other catalysis.\n2, as for the catalytic reactions, the substrate scope was not well studied. More challenging substrates\ncontaining reducible functional groups should be included. It was also unfortunate to display poor\ncatalytic activity towards general ester substrates.\nWe thank the reviewer for their comment regarding substrate scope. We have now addressed this issue\nand included more substrates which contain other reducible groups such as sulfones, esters, exo-cyclic\nolefins and amides (2p-2s). The spectroscopic data for this has been included in the supporting\ninformation. Regarding the inactivity of esters towards these conditions, we believe that highlighting\nthe limitations of this catalyst system is important and thus demonstrates the chemoselectivity of our\nprotocol, where we can tolerate substrates bearing esters.\nReviewer #3 (Remarks to the Author):\nThe article by Grose et al. describes an experimental and computational study into very interesting\niron boron chemistry for hydroboration of carbonyl containing compounds, and they describe the\nisolation of a unique iron(I) ketyl complex in an antiferromagnetic ground state. The manuscript is\nwell written and the topic is of high scientific interest.\nOverall the work is highly interesting both in terms of experiment and theory.\nI will focus my review on the computational work in this study and I ask the authors to consider the\ncomments below:\n1) In iron coordination compounds, the electronic structure may have a large flexibility in spin states\ndepending on the detailed surroundings. This is apparent in the intricate electronic structure found for\nantiferromagnetically coupled complex 9, but it will also play a role in the dinuclear N2-bridged\ncomplex A. Assuming S=1 for the two Fe centres, it is not obvious how the magnetic moments of the\ntwo iron centres are coupled and what the electronic ground-state structure looks like. Further, in\nterms of reaction kinetics and thermodynamics the concept of two-state or multi-state reactivity\ninvolving spin crossover steps is often relevant. Therefore the electronic structure of all Fe containing\nspecies must be carefully evaluated in order to ascertain the ground-state potential energy surface.\nAlso: The electronic structure of species A should be discussed in a little detail:\n- How are the two magnetic iron centres coupled?\n- Why are other spin multiplicities not considered or discussed?\n- How is the possibility of spin change across the PES excluded?\nIn Table S3, we have given the energies from the r2SCAN-3c geometry optimisations for each of the\nminima along the computed lowest energy reaction pathway with S=0,1,2 at each Fe centre. These\nresults clearly indicate that S=1 is consistently the lowest energy solution. Complex A used in this\nstudy was previously reported by Suess and Peters in 2015 (J. Am. Chem. Soc. 2013, 135, 4938–4941)\nin which they claim there is an antiferromagnetic coupling between the two S = 1 iron centres, with\nthe two pseudotetrahedral Fe centres each having different local geometries in the solid state.\n2) With regard to reactivity the entropic contributions cannot be neglected in my opinion. This is\nparticularly true for reaction steps involving the cleavage/formation of dimeric structures or, in\ngeneral, steps involving change in particle numbers.\nIn Figure 3, the updated text (with slightly updated values, where thermal enthalpic contributions have\nalso been included) now indicates that these are Gibbs free energy values, where the entropy\ncontribution is from translational entropy. An alternative free energy profile is given in the Supporting\nInformation (Figure S8), where vibrational and rotational entropy have also been included. In this\ncase, some of the early transition states’ energy barriers are raised, but the rate-limiting step stays\nclose to the same position (relative to A).\n3) I would be interested to learn more about the authors’ perspective on why the iron ketyl radical 9\nexhibits such unusual antiferromagnetic features. Are there particular properties of the iron-boron\ninteraction and/or the iron-carbonyl bond that govern the antiferromagnetic ground state? Or\nconversely, what inhibits this antiferromagnetic behaviour in other iron-ketyl compounds? Further\nelaboration would enhance the impact of the manuscript.\nIt would appear that the steric bulk of the group attached to the born-containing ligand, and the fact\nthat there are several phenyl groups in close proximity, allows the open-shell “singlet” behaviour (of\nthe antiferromagnetic coupled electrons, in addition to the two alpha spin electrons which give the\noverall S=1 spin state). While we can note that this exists with DFT, it would require further\ninvestigation with a multireference method (e.g. CASSCF/CASPT2). However, this would be\nchallenging given the number of interacting orbitals. As this was an off-cycle product rather than\ncentral to the catalytic process, we have (for now) decided not to investigate in further detail.\nFurther specific remarks\nMain text:\nComputational study of 9:\nHow does the computed molecular structure/geometry compare with that extracted from XRD?\nThe geometry of 9 was optimised directly from the XRD structure and has an RMSD of 0.34 Å. The\noverall structure matches qualitatively, with very minor differences in atomic positions, presumably as\na result of gas phase / condensed phase (calculations) vs. packing effects in the crystal structure.\nPlease report the relative energies of the neighbouring (pure) spin multiplicities, S=2 quintet and S=0\nclosed-shell singlet.\nThese are now reported in Table S3 in the Supporting Information.\nPlease state the isodensity value for the spin density plot in Figure 2d.\nThe figure caption has now been updated to include the isodensity value (which is 0.02 Å-3).\nPlease state the <S**2> value for 9 also somewhere in the main text (e.g. in the caption of Figure 2d).\nThe <S**2> value of 3.28 is now reported in the figure caption as recommended.\nThe spin populations (NPA or Mulliken) on the relevant atomic sites (Fe, B, Fe-coordinated phenyl,\nO, rest of the ketyl group) should be reported - in the ESI as appropriate.\nThese quantities are now reported in the Supporting Information. Three atoms have substantial spin\ndensity: Fe, B and the C (of the C=O group coordinated to Fe).\nEnergy profile for hydroboration:\nIt is not clear which energy values are reported for the computed potential energy surface:\nOn the y-axis of Figure 3 \"Delta-H + ZPE\" is given. This is a conflicting description. Delta-H would\nalready include ZPE. Perhaps \"Delta-E + ZPE\" is meant? Then these values would correspond to zero\nK data. Is this the case here?\nWe apologise for the confusing (and technically incorrect) labelling given here. These are Gibbs free\nenergy values, where the entropic term is taken from the translational entropy (as discussed above).\nPlease report Gibbs energies including entropy contributions at r.t. instead of just enthalpies (or\nenergies at zero K). This is particularly important for comparison with experiment and for assessment\nwhether a barrier height is rate limiting or not.\nPlease see comment above.\nIf I understand correctly, only the S=1 triplet spin surface is considered. Other spin multiplicities\nmight play a role here, and these should be investigated and discussed in the same detail (or excluded\nif applicable).\nThe energies for the optimised geometries with different spin multiplicities are now given in the\nSupporting Information (Table S3) with a sentence added to page 8 of the manuscript. In all cases, the\nS=1 per Fe centre is the lowest in energy,\nSupporting information:\nPlease report the corresponding transition wavelengths/energies of the TD-DFT results. How does the\ncomputed spectrum compare to the experimentally observed one?\nThe computed transition wavelengths are now given in the Supporting Information. The calculated\nwavelengths are 490 nm (c.f. expt. 522 nm) and 605 nm (c.f. expt. 652 nm). These are in reasonable\nagreement, given that explicit solvent hasn’t been used in the calculations.\nFigures S8-S10:\nIt is not clear which spin surface the PES refers to. Please report specifics on the electronic structure,\nat least the spin multiplicity of the species in the PES.\nThe Figure captions have been updated to reflect the S=1 spin multiplicity of the different\ncalculations.\nFor comparison with experiment, Gibbs free energies at r.t. should be reported instead of \"enthalpies\nplus ZPE\".\nPlease see comment(s) above.\nPlease carefully check and amend the References in the ESI.\nHere are two examples:\nReference 13 seems incomplete.\nThe authors' list in Reference 15 for the QChem package doesn't look right.\nReference 13 has been updated with an access date. Reference 15 has been updated with the first\nauthor’s name; however, as there are 220 authors on this paper, we have truncated the list using\nstandard notation (i.e. “et al.”).\nPlease include Cartesian coordinates, total energies and spin expectation values for all computed\nspecies.\nThe Cartesian coordinates have now been uploaded to the Supporting Information – as we responded\nto Reviewer 1 above, we apologise for accidentally omitting these. Total energies (from the ωB97X-\nD3/def2-TZVP calculations) and corresponding <S2> values are now given in Table S4 of the\nSupporting Information."}, {"round": 2, "reviewer_comments": {"reviewer_1": "The authors attempted to revise the manuscript in accordance with the reviewers' comments; however, the revisions and responses remain unsatisfactory.\n1. The monomeric Fe(I) species can exist as a doublet, quartet, or sextet. However, the authors calculated only the quintet and triplet states. What is the total charge of this complex? Did the authors also calculate the Fe(II) species? If not, this omission raises significant concerns about the analysis.\n2. According to the energy span model, the total barrier is calculated to be 26.2 kcal/mol, as noted in well-established literature within the field of computational catalysis (Accounts of Chemical Research, 2011, 44, 2, 101-110). There should be a more favorable reaction pathway that can satisfactorily account for the experimental observations. If the reaction occurs at room temperature, the barrier should ideally be below 25 kcal/mol.\n3. The proposed mechanism suggests a concerted transition state involving a four-membered ring. Notably, there is no indication of coordination or bonding interaction between the metal center and the substrate in this transition state. What is the actual role of the catalyst in this scenario? This appears to be an unprecedented form of catalysis. The authors may well achieve a similar barrier without the catalyst.", "reviewer_2": "The revised manuscript has been greatly improved and the authors' responses to reviewers further convinced this reviewer to recommend this manuscript to be accepted for publication.", "reviewer_3": "All questions and concerns have been addressed, and I believe that the article is sufficient for publication."}, "author_response": "The authors attempted to revise the manuscript in accordance with the reviewers'\ncomments; however, the revisions and responses remain unsatisfactory.\n1. The monomeric Fe(I) species can exist as a doublet, quartet, or sextet. However,\nthe authors calculated only the quintet and triplet states. What is the total charge of\nthis complex? Did the authors also calculate the Fe(II) species? If not, this omission\nraises significant concerns about the analysis.\nFrom the reviewer’s original comments (and that above), we’re not sure if they’re\nreferring to the ketyl radical (9, shown in Figure 2), or structures in the reaction profile\n(e.g. 11, 13, Figure 3 and Scheme 4). For the ketyl radical species (9), the SQUID data\nis suggestive of an antiferromagnetically coupled pair of electrons (one from iron and\none from the ketyl fragment) due to the curves not plateauing at the higher temperature\nregime, and two unpaired electrons on the iron centre (S = 1,  of 2.78). If the Fe is\neff\nin the +1 oxidation state i.e. d7 centre, with an antiferromagetic coupling to the ketyl\nradical, this will result in an S = 1 ground state. For an Fe(II) system (d6), with an\nantiferromagnetic coupling, then a Krämers doublet is possible, however this would\nresult in the observation of a signal in the EPR spectrum. When the EPR was\nperformed at X-, L- and K- band, both frozen and solution, no signals were observed,\nsuggesting that ketyl radical species 9 has a whole integer spin rather than a non-\ninteger spin.\nThis would also be true for 11 and 13 as well. The overall charge (in each case) is\nneutral, such that the total number of electrons is even, hence doublets, quartets etc\nare not possible, in line with the experimental evidence (SQUID + EPR). We have\ngiven energies calculated for the different spin states of the reaction profile (singlets,\ntriplets and quintets) in Table S3 of the Supporting Information.\n2. According to the energy span model, the total barrier is calculated to be 26.2\nkcal/mol, as noted in well-established literature within the field of computational\ncatalysis (Accounts of Chemical Research, 2011, 44, 2, 101-110). There should be a\nmore favorable reaction pathway that can satisfactorily account for the experimental\nobservations. If the reaction occurs at room temperature, the barrier should ideally\nbe below 25 kcal/mol.\nThe values presented in Figure 3 are all relative to A and are calculated using ΔE +\nZPE + translational entropy correction, to give an approximate ΔG value (this is\ndescribed in Figure 3 and the computational details in the Supporting Information). In\nFigure S8 (Supporting Information), we present the reaction profile using all enthalpy\nand entropy corrections from the implicit solvation model in the calculation of ΔG,\nleading to a barrier height of 18.3 kcal mol-1 (consistent with the reviewer’s\nsuggestion of the energy span model). The other pathways considered all have\nbarrier heights in excess of 30 kcal mol-1, irrespective of which definition of ΔG is\nused.\n3. The proposed mechanism suggests a concerted transition state involving a four-\nmembered ring. Notably, there is no indication of coordination or bonding interaction\nbetween the metal center and the substrate in this transition state. What is the actual\nrole of the catalyst in this scenario? This appears to be an unprecedented form of\ncatalysis. The authors may well achieve a similar barrier without the catalyst.\nThe mechanism we have proposed shows a stepwise formation of the product: in the\nfirst transition state, the B(HBpin) – O(ketone) bond is formed, followed by the\nsecond transition state in which hydride transfer from the Bpin to carbon occurs. The\nFe centre plays a role in formation of the initial B-O bond, by increasing the Lewis\nacidity of the boron centre upon coordination of HBpin (11), allowing the ketone to\nreact to form the intermediate (labelled as ts_11-13_int.xyz in the supporting data)\nwhich goes to the rate determining transition state. In this transition state, steric\nattraction supports the hydride transfer resulting in a lowering of the energy barrier\nfor this process (relative to the uncatalysed reaction). In the manuscript, this is\ndescribed on page 8 (first paragraph of “DFT studies”), which notes that the\nuncatalysed reaction is ~5 kcal mol-1 higher than the catalysed reaction.\nFrom an experimental viewpoint, no reaction occurs in the absence of the Fe(0)\nspecies over the 5-hour time frame for this substrate. Based on our observations, we\nbelieve the role of the catalyst is to weaken the B–H bond to facilitate the hydride\ntransfer.\nIn the DFT section of the manuscript, we have broken the text up so that it is not\nsuggestive of a concerted pathway for the transfer of the boron to oxygen and the\nhydride addition step."}, {"round": 3, "reviewer_comments": {"reviewer_1": "The authors have properly addressed my questions and concerns, and the article can be accepted for publication."}, "author_response": ""}]

Decision letter