Ligand-free iron carbonyl catalyzed transfer hydrogenation strategy: synthesis of N-heterocycles

Abstract

Transfer hydrogenation (TH) systems have been extensively developed using a variety of metal catalysts. Herein, we report a ligand-free TH protocol that proceeds via iron carbonyl complex catalysis for the efficient synthesis of diverse N-heterocycles. Using benzyl alcohol and 2-nitrobenzamide, quinazolinone scaffolds were obtained in high yields via TH with subsequent condensation and annulation steps. Notably, 2-nitrobenzonitriles can also be converted into quinazolinones using this protocol. Furthermore, the method was successfully applied to the synthesis of other heterocycles, benzoxazoles and pyrrolo[1,2-α]quinoxalines. The protocol is operationally simple, cost-effective and does not require auxiliary ligands, providing a sustainable route to complex N-heterocycles. Control experiments suggested that molecular hydrogen is generated during alcohol oxidation and participates in the subsequent reduction of nitro groups to amines. DFT calculations supported a mechanism in which an iron tricarbonyl complex mediates hydrogen transfer, facilitating the generation of molecular hydrogen from benzyl alcohol.

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Introduction

Transfer hydrogenation (TH) systems have emerged as a powerful method for reducing π bond-containing functional groups.^1–3 Classical hydrogenation methods typically use hydrogen gas in combination with transition metal catalysts. However, due to the flammability and difficulties in handling molecular hydrogen, alternative processes have been developed. Among such systems, TH systems utilize external hydrogen donors, which are oxidized while the hydrogen acceptors are reduced.^4–6 Alcohols are the most commonly used donors for TH because of their low cost and experimental convenience.^7–9 Conventional hydrogen acceptors include olefins, carbonyls and imines, which are readily available in a broad range of synthetic compounds.^10–14

Hydrogen transfer is typically facilitated by the use of metal catalysts, and various metal complexes have been developed for TH systems (Scheme 1A).^15,16 A significant portion of these systems employ ligand–metal bifunctional catalysts.^17–20 One of the earliest noble metal catalysts for TH was developed by Shvo in 1985, which enabled the hydrogenation of ketones using alcohols as hydrogen donors.²¹ In Shvo-type catalysts, a cyclopentadienone ligand bound to a ruthenium center temporarily accommodates a hydrogen atom during the reaction, playing a crucial role in the overall mechanism (Scheme 1B).^22,23 On the basis of this framework, similar metal complexes, such as those incorporating Os,^24,25 Ir,²⁶ and Mo,²⁷ have been developed. However, the use of noble metals remains expensive and is associated with environmental concerns. As a result, base transition metals have gained significant attention. Iron has emerged as a particularly attractive candidate owing to its high natural abundance and low toxicity. (Cyclopentadienone)iron(0) carbonyl (CIC) complexes serve as iron-based analogs of the Shvo catalyst, as they also feature a cyclopentadienone ligand essential for catalytic activity.^28,29 In addition to catalyst development, many researchers have adopted a strategy in which an oxidized hydrogen donor is incorporated into coupling reactions. For example, Barta and Sundararaju developed a C–N coupling methods using CIC complexes (Scheme 2A).^30,31 In this system, the generated carbonyls participate in condensation with amine nucleophiles and form imine intermediates, which can further undergo hydrogenation for C–N bond coupling. CIC complexes are synthesized from iron carbonyl complexes through the incorporation of a cyclopentadienone ligand (Scheme 2B);³² however, the requirement for pre-synthesis remains both labor intensive and operationally inconvenient. Moreover, the synthesis of the cyclopentadienone ligand typically involves multiple steps, and the catalytic activity is often dependent on the preparation method. Therefore, developing simpler and more practical catalyst systems that offer benefits in terms of synthetic efficiency and practical convenience, is highly important. However, the direct use of simple iron carbonyls without pre-synthesized ligands in TH remains unexplored.

Scheme 1 Various metal-centered catalysts for TH systems.

Scheme 2 Synthetic approaches for N-heterocycle formation.

Previously, our group discovered nitroarenes as efficient hydrogen acceptors and employed them in TH systems with alcohols using a CIC complex.^33–38 The TH process generates an aldehyde and an amine intermediate, and their condensation results in intermolecular C–N bond coupling. Owing to the ortho-nucleophile on nitroarenes, this methodology has been successfully extended to the synthesis of various N-heterocycles, which are key structural motifs in small-molecule drugs and natural products (Scheme 2A-3). Motivated by these results, we sought to develop a TH system using iron carbonyl complexes that do not rely on complex ligand synthesis. Iron carbonyl complexes are readily available and precursors of CIC complexes, making them highly attractive, synthetically efficient alternatives for TH systems (Scheme 2B). Organometallic reactions utilizing iron carbonyl complexes in the absence of additional ligands have not yet been reported, highlighting the novelty and unexplored potential of such systems. Herein, we report an alternative TH system with alcohols and nitro compounds employing a ligand-free iron carbonyl complex. This method is cost-effective, free of auxiliary ligands, and operationally simple for the one-pot synthesis of various N-heterocycles (Scheme 2C).

Results and discussion

To evaluate our hypothesis, we first examined the iron carbonyl-catalyzed TH conditions for the in situ generation of imines using benzyl alcohol as the hydrogen donor and nitrobenzene as the hydrogen acceptor (Table 1). Considering the hydrogen atom balance, we set the initial molar ratio of nitrobenzene to benzyl alcohol at 1 : 3. To assess catalytic performance, we tested several iron carbonyl complexes with the comparative CIC complex. Trimethylamine-N-oxide (TMAO) was added as an activator for the catalyst, and the reactions were conducted in cyclopentyl methyl ether (CPME) at 160 °C for 48 h. Under these conditions, the desired imine products were obtained in moderate yields, indicating that iron carbonyl complexes are capable of facilitating TH (entries 2–4).

Table 1 Screening iron catalysts for the reaction between nitrobenzene and benzyl alcohol

Entry	Catalyst (mol %)	Yield^a (%)
Reaction conditions: nitrobenzene (0.3 mmol), benzyl alcohol (0.9 mmol), Fe cat. (x mol%), TMAO (2x mol%) and CPME (1.0 mL) in a sealed tube under argon for 48 h at 160 °C.a Yields determined by ^1H NMR using 1,3,5-trimethoxybenzene as the internal standard.
1	Knölker complex (10)	51
2	Fe(CO)5 (10)	53
3	Fe2(CO)9 (5)	68
4	Fe3(CO)12 (3)	31
5	—	N.R.

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Inspired by the reactivity of iron carbonyl catalysts, we aimed to design an N-heterocycle synthetic route via the TH strategy. Our particular focus was the quinazolinone scaffold, which holds a prominent position in pharmaceutical research owing to its role as a key building block in diverse drug molecules.^39–41 In nitrobenzene substrates bearing an amide group at the ortho position, in situ imine formation is followed by intramolecular annulation via C–N bond formation, and subsequent oxidation was expected to afford the quinazolinone framework. Using the conditions in Table 1, N-methyl-2-nitrobenzamide and benzyl alcohol were selected as model substrates (Table 2). We first screened iron carbonyl catalysts to identify the most effective system (entries 1–4). The desired product 3aa was obtained along with its unoxidized intermediate 3aa′, and Fe₃(CO)₁₂ facilitated the best combined yield of 82% under conditions with the same molar amount of iron (entry 4). We next investigated the effect of alcohol equivalents, hypothesizing that 3aa′ might serve as a secondary hydrogen donor during further oxidation to 3aa. Reducing the amount of benzyl alcohol to 2 equivalents led to increased selectivity for 3aa formation (entry 5), whereas a further decrease to 1.5 equivalents significantly lowered the overall yields of 3aa and 3aa′, suggesting insufficient hydrogen transfer (entry 6). Subsequent screening of solvents revealed that toluene afforded the highest yield and selectivity for 3aa (entries 7–9). Increasing the reaction concentration to 1 M further improved the efficiency, affording 3aa in 91% yield (entry 10). Using an equivalent amount of TMAO relative to the catalyst resulted in insufficient reactivity (entry 11), whereas employing three equivalents provided a yield similar to that obtained with two equivalents (entry 12). Accordingly, 6 mol% of TMAO was selected as the optimal condition to ensure reaction efficiency. As expected, the reaction did not proceed in the absence of the iron catalyst, confirming that the iron carbonyl catalyst is essential for the TH process (entry 13).

Table 2 Optimization of the synthesis of quinazolinones

Entry	Catalyst	2a (equiv.)	Solvent	3aa	3aa′
Reaction conditions: 1a (0.3 mmol), 2a, Fe cat. (3 mol%), TMAO (6 mol%) and solvent (1.0 mL) in a sealed tube under argon for 48 h at 160 °C. Yields of the isolated products.a Fe cat. (10 mol%), TMAO (20 mol%).b Fe cat. (5 mol%), TMAO (10 mol%).c PhMe (0.3 mL).d TMAO 3 mol%.e TMAO 9 mol%.
1^a	Knölker complex	3	CPME	27	30
2^a	Fe(CO)5	3	CPME	49	19
3^b	Fe2(CO)9	3	CPME	55	19
4	Fe3(CO)12	3	CPME	63	19
5	Fe3(CO)12	2	CPME	61	6
6	Fe3(CO)12	1.5	CPME	57	2
7	Fe3(CO)12	2	Xylene	51	9
8	Fe3(CO)12	2	PhCl	77	—
9	Fe3(CO)12	2	Toluene	80	—
10	Fe3(CO)12	2	Toluene^c	91	—
11^d	Fe3(CO)12	2	Toluene^c	73	—
12^e	Fe3(CO)12	2	Toluene^c	91	—
13	none	2	Toluene^c	N. R.	—

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With the optimized conditions in hand, a variety of substituted substrates were evaluated for the quinazolinones (Scheme 3). Benzylic alcohols with diverse substituents were efficiently coupled with 1a to afford the corresponding quinazolinone products 3aa–3ap in good yields. Most of the tested benzyl alcohols with simple substituents were well tolerated, and no significant dependence on the substituent position or electronic nature was observed. In the case of the methyl ester substituent, the corresponding product 3aj was obtained in lower yield, likely due to competitive transesterification with the benzylic alcohol. The boronic ester-substituted benzyl alcohol substrate also afforded the desired product 3ak in lower yield, with the starting material remaining in the reaction mixture. In addition to simple phenyl derivatives, naphthyl and heteroaromatic groups could also be successfully introduced at the C2 position of the quinazolinone moiety (3aq–3av). Furthermore, the use of allylic and propargylic alcohols resulted in the incorporation of unsaturated side chains (3aw–3ax). In the case of propargylic alcohols, no partially reduced byproducts were detected. Rather, the starting material and corresponding alcohol were largely recovered, even after extended reaction times. This outcome indicates that the C–C π bond is preserved under our transfer hydrogenation conditions. In contrast, reactions with aliphatic alcohols provided the desired products 3ay–3az in lower yields, with the unreacted alcohol indicating insufficient efficiency for the TH process. Notably, the use of cyclohexanol as a hydrogen donor afforded the spirocyclic quinazolinone 3aaa. The practical utility of the developed method was demonstrated by the gram-scale (5.6 mmol) synthesis of 3aa, which afforded the product in 80% yield. Next, we examined a series of N-substituted-2-nitrobenzamides to further extend the substrate scope (Scheme 3), and the amide substituent was systematically replaced with various groups. Unsubstituted and alkyl-, allyl-, and benzyl-substituted amide derivatives were well tolerated, affording the corresponding quinazolinones 3ba–3ha in good to moderate yields, except for the low yield of the isopropyl-substituted product 3fa, which was likely due to increased steric hinderance. Like those bearing an isopropyl group, the aryl-substituted amides also afforded the products 3ia and 3ja in decreased yield. These results suggest that sterically demanding substituents on the amide nitrogen led to decreased efficiency. We also investigated the scope of 2-nitrobenzamide substrates with substituents on the aryl ring. Substrates with substituents at the 4- and 5-positions of the phenyl ring were transformed into products 3ka–3pa in high yields independent of electronic effects or the position of the substituents. However, the use of a pyridine moiety instead of a phenyl group resulted in a decreased yield (3qa).

Scheme 3 Scope of the reaction of quinazolinones with N-methyl-2-nitrobenzamide. Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), Fe₃(CO)₁₂ (3 mol%), TMAO (6 mol%) and PhMe (0.3 mL) in a sealed tube under argon for 48 h at 160 °C. Yields of the isolated products. ^a 2 (0.9 mmol).

On the basis of our developed protocol, we next sought to utilize nitrile-containing substrates as starting materials (Scheme 4). Our initial strategy was based on the idea that if the nitrile undergoes hydrolysis to generate an amide during the reaction, a similar process could lead to the formation of quinazolinones. However, when the optimized conditions were applied to 2-nitrobenzonitriles, significantly lower yields were observed (see the SI, Tables S1 and S5). We hypothesized that the addition of a basic additive might serve as a driving force for in situ amide formation of nitriles. In contrast, the addition of base led to further reductions in yield. Instead, increasing the catalyst loading from 3 mol% to 6 mol% improved the outcome, affording the desired product in 66% yield, which is slightly lower than that of the corresponding amide reaction (vs.3ba in Scheme 3). We then examined the substrate scope for quinazolinone synthesis using 2-nitrobenzonitrile (Scheme 4). Although most substrates exhibited lower reactivity than their amide analogs did, they demonstrated good functional group tolerance and acceptable yields across a variety of benzyl alcohols and 2-nitrobenzonitrile substrates.

Scheme 4 Scope of the reaction of quinazolinones with 2-nitrobenzonitriles. Reaction conditions: 4 (0.3 mmol), 2 (0.6 mmol), Fe₃(CO)₁₂ (6 mol%), TMAO (12 mol%) and PhMe (1.0 mL) in a sealed tube under argon for 48 h at 160 °C. Yields of the isolated products.

To highlight the synthetic versatility of our developed catalytic method, we further derivatized the quinazolinone products through post-functionalization of key substituents (Scheme 5, see the SI for synthetic details, S40–44). First, the reaction between 2-nitrobenzamide and 1H-indole-2-methanol efficiently delivered compound 3bab in a single step, which underwent formylation to furnish the natural alkaloid bouchardatine, an inhibitor of adipogenesis and lipogenesis.^42,43 Next, quinazolinone 3rb was transformed into compound 11, which possesses anti-inflammatory activity,⁴⁴ through thiation at the 4-position followed by S-alkylation. Finally, compound 12, which has potent antiproliferative effects, was synthesized via Heck coupling from quinazolinone 3dac.⁴⁵

Scheme 5 Derivation using the synthesized quinazolinones.

To further demonstrate the utility of our ligand-free iron-catalyzed TH system, we extended our work to the synthesis of other heterocycles. On the basis of the previously reported benzoxazole synthesis system using a CIC complex,³⁴ we applied Fe₃(CO)₁₂ as a catalyst instead of the CIC complex. Notably, the reaction in xylene afforded the desired benzoxazole product in 76% yield, slightly higher than 72% yield with toluene. The substrate scope for benzoxazole generation was also investigated (Scheme 6). Various substituted 2-nitrophenols and benzyl alcohols provided the desired benzoxazole products in good to moderate yields.

Scheme 6 Scope of the reaction for benzoxazoles and pyrrolo[1,2-α]quinoxalines. ^a Reaction conditions for benzoxazoles: 5 (0.30 mmol), 2 (0.45 mmol), Fe₃(CO)₁₂ (3 mol%), TMAO (6 mol%) and o-xylene (1.0 mL) in a sealed tube under argon for 24 h at 160 °C. Yields of the isolated products. ^b Reaction conditions for pyrrolo[1,2-α]quinoxalines: 7 (0.30 mmol), 2 (0.60 mmol), Fe₃(CO)₁₂ (4 mol%), TMAO (8 mol%) and CPME (1.0 mL) in a sealed tube under argon for 48 h at 160 °C. Yields of the isolated products.

We next focused on pyrrolo[1,2-α]quinoxalines, another class of N-heterocycles. In a previous protocol involving the CIC complex, the cyclization of 1-(2-nitrophenyl)pyrrole and benzyl alcohol was conducted under an oxygen atmosphere to facilitate the final oxidation step.³⁷ However, under the same aerobic conditions, the Fe₃(CO)₁₂ catalytic system failed to deliver the desired product (see the SI, Tables S2 and S5). By switching to an argon atmosphere and increasing both the catalyst loading and reaction time, we successfully obtained pyrrolo[1,2-α]quinoxaline in 90% yield. Then, the substrate scope for the synthesis of pyrrolo[1,2-α]quinoxalines was examined (Scheme 6). All the substituted 1-(2-nitrophenyl)pyrroles and benzyl alcohols afforded quinoxaline products in high yields. On the basis of these results, we are confident that the developed ligand-free iron carbonyl catalytic system can serve as a promising alternative to the CIC complex, which is widely used in various TH transformations.

To gain insight into the reaction mechanism, a systematicmechanistic study was performed. On the basis of the general TH system, we hypothesized that the benzyl alcohol acts as a hydrogen donor, transferring hydrogen to the iron carbonyl complex, which subsequently delivers the hydrogen to the nitro group. However, whereas ligand–metal bifunctional complexes such as the CIC complex operate via well-established catalytic cycles, the reactivity profile and active species of iron carbonyl complexes without additional ligands remain unclear.

To examine whether a hydrogen acceptor is essential for alcohol oxidation, a reaction was conducted using only benzyl alcohol and Fe₃(CO)₁₂ in the absence of a nitro compound (Scheme 7A-1). Under these conditions, benzyl alcohol was oxidized, indicating that alcohol oxidation can proceed independently of an external acceptor. This observation suggests that TH likely proceeds via a stepwise mechanism rather than a concerted pathway. To further evaluate the source and role of hydrogen, a two-stage experiment was performed (Scheme 7A-2): a mixture of benzyl alcohol and Fe₃(CO)₁₂ was first reacted in a sealed tube. After 24 h, the seal was removed, and nitrobenzene was added. This sequential addition resulted in the formation of the desired product in only 8% yield, suggesting that the molecular hydrogen generated during alcohol oxidation had dissipated before it could reduce the nitro compound. In a separate experiment (Scheme 7A-3), the reduction of 1a by molecular hydrogen alone in the presence of Fe₃(CO)₁₂ resulted in the successful formation of the corresponding aniline, supporting the hypothesis that Fe₃(CO)₁₂ can mediate hydrogen transfer from H₂ in the reaction vessel. In contrast, no reaction occurred in the absence of Fe₃(CO)₁₂, further highlighting its essential role in the transformation. To further probe the formation of hydrogen gas, a mixture of benzyl alcohol and Fe₃(CO)₁₂ was stirred in a flask connected to another Schlenk flask containing styrene (Scheme 7A-4, see the SI, Fig. S1 and S55).⁴⁶ The formation of ethylbenzene in the styrene flask confirmed that molecular hydrogen was generated in situ, which is consistent with a two-step TH mechanism involving alcohol oxidation followed by hydrogenation of the nitro compound via molecular hydrogen.

Scheme 7 Mechanistic studies of TH process. ^a Yields determined by ¹H NMR using internal standards. ^b All DFT calculations were conducted with Gaussian 16 M06-2X/def2-TZVP-SMD(PhMe)//M06-2X/def2-SVP.

To gain mechanistic insights into the hydrogen transfer process mediated by iron carbonyl complexes, we carried out density functional theory (DFT) calculations to estimate the energy landscape of key intermediates and transition states (Scheme 7B and C). The oxidation of benzyl alcohol and the reduction of nitrobenzene were chosen as representative model systems. Although Fe₃(CO)₁₂ was used experimentally as the catalyst, it is known to degrade into a monomer under thermal conditions; thus, Fe(CO)₄ was employed as the computationally tractable active species. Our initial hypothesis involved the insertion of Fe(CO)₄ into the O–H bond of benzyl alcohol. However, this pathway exhibited no energetically feasible transition state (TS1C). Alternatively, the oxidative addition of Fe(CO)₄ to the benzylic C–H bond resulted in an energy barrier of 32.6 kcal mol⁻¹, indicating limited reactivity (TS1B). In the presence of TMAO, CO is oxidized to CO₂ and escapes from Fe(CO)₄, generating the less saturated complex Fe(CO)₃, which has a significantly lower C–H oxidative addition barrier of 20.9 kcal mol⁻¹ (TS1A). Further stabilization occurs through coordination of the aromatic ring, forming an η³-ligand coordination framework. In this geometry, oxidative addition proceeds with a barrier of 10.7 kcal mol⁻¹, resulting in a net barrier of 25.5 kcal mol⁻¹ for alcohol activation (TS1). The iron–hydride intermediate subsequently abstracts a proton from the alcohol O–H bond. As the transformation progresses, the iron center bound in an η³-benzylic configuration moves to the benzylic position, which results in an energy barrier of 22.6 to 17.9 kcal mol⁻¹ (TS2 compared with TS2A). This sequence ultimately leads to the generation of benzaldehyde and molecular hydrogen while regenerating Fe(CO)₃. In the next step, nitrobenzene coordinates to Fe(CO)₃ with one of its oxygen atoms (TS3). The molecular hydrogen interacts with both the iron center and the distal nitro oxygen to form IM4, in which each hydrogen atom is held near the respective acceptor atoms, with a total energy barrier of 21.4 kcal mol⁻¹. Following the formation of IM4, the nitrogen atom engages in intramolecular hydrogen transfer with the remaining hydride ligand (TS4), liberating Fe(CO)₃ and forming IM5. Finally, proton shift and dehydration results in nitroso compound generation. This nitroso compound undergoes two consecutive hydrogenation steps, ultimately being reduced to the corresponding aniline.

Conclusions

In summary, we have developed a ligand-free TH system mediated by iron carbonyl complexes that employ benzyl alcohol as the hydrogen donor and a nitro group as the hydrogen acceptor. This method enables the efficient synthesis of quinazolinone scaffolds via in situ annulation and condensation sequences. In addition, other N-heterocycles, such as benzoxazoles and pyrrolo[1,2-α]quinoxalines, were successfully synthesized using this cost-effective, ligand-free protocol. DFT calculations were carried out to elucidate the mechanistic features of the iron carbonyl-mediated TH process, which provided insights into alcohol activation and nitro group reduction.

Author contributions

J. Hong: contributed to conceptualization, investigation, methodology, and conducted the majority of the experimental work, data analysis, computational mechanistic studies; S. B. Lee, S. H. Choi, J. Lee, H. Lee, and J. Jang: conducted the minority of the experimental work and primary data acquisition; S. Hong: supervised the project and acquired funding. The manuscript was written by J. Hong, and reviewed by S. Hong. All authors have given approval to the final version of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Data availability

Supplementary information (SI): all experimental procedures, characteriazation data, computational details, Cartesian coordinates of optimized geometries, ¹H and ¹³C NMR spectra. See DOI: https://doi.org/10.1039/d5qo01274k.

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00218616 and RS-2024-00351679).

References

1. G. E. Dobereiner and R. H. Crabtree, Dehydrogenation as a substrate-activating strategy in homogeneous transition-metal catalysis, Chem. Rev., 2010, 110, 681–703.
2. C. Gunanathan and D. Milstein, Applications of acceptorless dehydrogenation and related transformations in chemical synthesis, Science, 2013, 341, 1229712.
3. D. Wang and D. Astruc, The golden age of transfer hydrogenation, Chem. Rev., 2015, 115, 6621–6686.
4. D. Gong, D. Kong, Y. Li, C. Gao and L. Zhao, Ni(II)-catalyzed transfer hydrogenation of azoarenes with NH₃BH₃, Org. Lett., 2023, 25, 4198–4202.
5. I. Khan, B. G. Reed-Berendt, R. L. Melen and L. C. Morrill, FLP-catalyzed transfer hydrogenation of silyl enol ethers, Angew. Chem., Int. Ed., 2018, 57, 12356.
6. Z. Shao, S. Fu, M. Wei, S. Zhou and Q. Liu, Mild and selective cobalt-catalyzed chemodivergent transfer hydrogenation of nitriles, Angew. Chem., Int. Ed., 2016, 55, 14653.
7. K. M. Waldie, K. R. Flajslik, E. McLoughlin, C. E. D. Chidsey and R. M. Waymouth, Electrocatalytic alcohol oxidation with ruthenium transfer hydrogenation catalysts, J. Am. Chem. Soc., 2017, 139, 738–748.
8. S. K. Murphy and V. M. Dong, Enantioselective ketone hydroacylation using Noyori's transfer hydrogenation catalyst, J. Am. Chem. Soc., 2013, 135(15), 5553–5556.
9. T. Ikariya and A. J. Blacker, Asymmetric transfer hydrogenation of ketones with bifunctional transition metal-based molecular catalysts, Acc. Chem. Res., 2007, 40, 1300–1308.
10. S. E. Sloane, A. Reyes, Z. P. Vang, L. Li, K. T. Behlow and J. R. Clark, Copper-catalyzed formal transfer hydrogenation/deuteration of aryl alkynes, Org. Lett., 2020, 22, 9139–9144.
11. H. Bauer, K. Thum, M. Alonso, C. Fischer and S. Harder, Alkene transfer hydrogenation with alkaline-earth metal catalysts, Angew. Chem., Int. Ed., 2019, 58, 4248.
12. M. Espinal-Viguri, S. E. Neale, N. T. Coles, S. A. Macgregor and R. L. Webster, Room temperature iron-catalyzed transfer hydrogenation and regioselective deuteration of carbon−carbon double bonds, J. Am. Chem. Soc., 2019, 141(1), 572–582.
13. M. Rueping, E. Sugiono, C. Azap, T. Theissmann and M. Bolte, Enantioselective brønsted acid catalyzed transfer hydrogenation: organocatalytic reduction of imines, Org. Lett., 2005, 7, 3781–3783.
14. S. Hoffmann, A. M. Seayad and B. List, A powerful brønsted acid catalyst for the organocatalytic asymmetric transfer hydrogenation of imines, Angew. Chem., Int. Ed., 2005, 44, 7424–7427.
15. J. Ito and H. Nishiyama, Recent topics of transfer hydrogenation, Tetrahedron Lett., 2014, 55, 3133–3146.
16. J. Itoh, S. Han and M. Krische, Enantioselective allylation, crotylation, and reverse prenylation of substituted isatins: iridium-catalyzed C-C bond-forming transfer hydrogenation, Angew. Chem., Int. Ed., 2009, 48, 6313–6316.
17. T. Zweifel, J. Naubron, T. Bϋttner, T. Ott and H. Grϋtzmacher, Ethanol as hydrogen donor: highly efficient transfer hydrogenations with rhodium(I) amides, Angew. Chem., Int. Ed., 2008, 47, 3245–3249.
18. S. K. Gediya, G. J. Clarkson and M. Wills, Asymmetric transfer hydrogenation: dynamic kinetic resolution of α-amino ketones, J. Org. Chem., 2020, 85, 11309–11330.
19. K. Muñiz, Bifunctional metal–ligand catalysis: hydrogenations and new reactions within the metal–(Di)amine scaffold, Angew. Chem., Int. Ed., 2005, 44, 6622–6627.
20. A. Matsunami, M. Ikeda, H. Nakamura, M. Yoshida, S. Kuwata and Y. Kayaki, Accessible bifunctional oxy-tethered ruthenium(II) catalysts for asymmetric transfer hydrogenation, Org. Lett., 2018, 20, 5213–5218.
21. D. Czarkie, Y. Rahamim and Y. Shvo, A new group of ruthenium complexes: structure and catalysis, J. Am. Chem. Soc., 1986, 108, 7400–7402.
22. B. L. Conley, M. K. Pennington-Boggio, E. Boz and T. J. Williams, Discovery, applications, and catalytic mechanisms of Shvo's catalyst, Chem. Rev., 2010, 110, 2294–2312.
23. S. E. Clapham, A. Hadzovic and R. H. Morris, Mechanisms of the H₂-hydrogenation and transfer hydrogenation of polar bonds catalyzed by ruthenium hydride complexes, Coord. Chem. Rev., 2004, 248, 2201–2237.
24. M. R. Burke, T. Funk and J. Takats, Photochemical reaction of Os₃(CO)₁₂ with diphenylacetylene: synthesis and structure of tricarbonyl-(η⁴-2,3,4,5-tetraphenylcyclopenta-2,4-dien-l-one)osmium, Organometallics, 1994, 13, 2109–2112.
25. J. Washington, R. McDonald and J. Takats, J. Os(CO)₄(η²-C₂Me2)-promoted coupling of alkynes and CO: Formation of (η⁴-C₄Me₂R₂CO)Os(CO)₃ (R = Me, Et, ⁿPr) and catalytic activity of (η⁴-C₄R₄CO)Os(CO)₃ (R = Me, Ph), Organometallics, 1995, 14, 3996–4003.
26. S. Kusumoto and K. Nozaki, Direct and selective hydrogenolysis of arenols and aryl methyl ethers, Nat. Commun., 2015, 6, 6296.
27. W. Wu, T. Seki, K. L. Walker and R. M. Waymouth, Transfer hydrogenation of aldehydes, allylic alcohols, ketones, and imines using molybdenum cyclopentadienone complexes, Organometallics, 2018, 37, 1428–1431.
28. H. Knölker, E. Baum, H. Goesmann and R. Klauss, Demetalation of tricarbonyl(cyclopenta dienone)iron complexes initiated by a ligand exchange reaction with NaOH - X-ray analysis of a complex with nearly square-planar coordinated sodium, Angew. Chem., Int. Ed., 1999, 38, 13–14.
29. A. Quintard and J. Rodriguez, Iron cyclopentadienone complexes: discovery, properties, and catalytic reactivity, Angew. Chem., Int. Ed., 2014, 53, 4044–4055.
30. T. Yan, B. L. Feringa and K. Barta, Iron catalysed direct alkylation of amines with alcohols, Nat. Commun., 2014, 5, 5602.
31. B. Emayavaramban, M. Sen and B. Sundararaju, Iron-catalyzed sustainable synthesis of pyrrole, Org. Lett., 2017, 19, 6–9.
32. G. N. Schrauzer, Diphenyl acetylene derivatives of iron carbonyl, J. Am. Chem. Soc., 1959, 81, 5307–5310.
33. R. R. Putta, S. Chun, S. B. Lee, D. Oh and S. Hong, Iron-catalyzed acceptorless dehydrogenative coupling of alcohols with aromatic diamines: selective synthesis of 1,2-disubstituted benzimidazoles, Front. Chem., 2020, 8, 429.
34. R. R. Putta, S. Chun, S. H. Choi, S. B. Lee, D. Oh and S. Hong, Iron(0)-catalyzed transfer hydrogenative condensation of nitroarenes with alcohols: a straightforward approach to benzoxazoles, benzothiazoles, and benzimidazoles, J. Org. Chem., 2020, 85, 15396–15405.
35. R. R. Putta, S. Chun, S. B. Lee, J. Hong, D. Oh and S. Hong, Iron-catalyzed one-pot synthesis of quinoxalines: transfer hydrogenative condensation of 2-nitroanilines with vicinal diols, RSC Adv., 2021, 11, 18225–18230.
36. R. R. Putta, S. Chun, S. B. Lee, J. Hong, S. H. Choi, D. Oh and S. Hong, Chemoselective α-alkylation and α-olefination of arylacetonitriles with alcohols via iron-catalyzed borrowing hydrogen and dehydrogenative coupling, J. Org. Chem., 2022, 87, 16378–16389.
37. S. Chun, J. Ahn, R. R. Putta, S. B. Lee, D. Oh and S. Hong, Direct synthesis of pyrrolo[1,2-α]quinoxalines via iron-catalyzed transfer hydrogenation between 1-(2-Nitrophenyl)pyrroles and alcohols, J. Org. Chem., 2020, 85, 15314–15324.
38. S. Chun, R. R. Putta, J. Hong, S. H. Choi, D. Oh and S. Hong, Iron-catalyzed transfer hydrogenation: divergent synthesis of quinolines and quinolones from ortho-nitrobenzyl alcohols, Adv. Synth. Catal., 2023, 365, 3367–3374.
39. X. Shang, S. L. Morris-Natschke, Y. Liu, X. Guo, X. Xu, M. Goto, J. Li, G. Yang and K. Lee, Biologically active quinoline and quinazoline alkaloids part I, Med. Res. Rev., 2018, 38, 775–828.
40. X. Shang, S. L. Morris-Natschke, G. Yang, Y. Liu, X. Guo, X. Xu, M. Goto, J. Li, J. Zhang and K. Lee, Biologically active quinoline and quinazoline alkaloids part II, Med. Res. Rev., 2018, 38, 1614–1660.
41. U. A. Kshirsagar, Recent developments in the chemistry of quinazolinone alkaloids, Org. Biomol. Chem., 2015, 13, 9336–9352.
42. Y. Rao, H. Liu, L. Gao, H. Yu, J. Tan, T. Ou, S. Huang, L. Gu, J. Ye and Z. Huang, Discovery of natural alkaloid bouchardatine as a novel inhibitor of adipogenesis/lipogenesis in 3T3-L1 adipocytes, Bioorg. Med. Chem., 2015, 23, 4719–4727.
43. K. Kim, H. Y. Kim and K. Oh, ortho-Naphthoquinone-catalyzed aerobic oxidation of amines to fused pyrimidin-4(3H)-ones: a convergent synthetic route to bouchardatine and sildenafil, RSC Adv., 2020, 10, 31101.
44. A. S. El-Azab, M. A. Al-Omar, A. A.-M. Abdel-Aziz, N. I. Abdel-Aziz, M. A.-A. El-Sayed, A. M. Aleisa, M. M. Sayed-Ahmed and S. G. Abdel-Hamide, Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: molecular docking study, Eur. J. Med. Chem., 2010, 45, 4188–4198.
45. R. Bollu, S. Banu, S. Kasaboina, R. Bantu, L. Nagarapu, S. Polepalli and N. Jain, N. Potential anti-proliferative agents from 1,4-benzoxazinone-quinazolin-4 (3H)-one templates, Bioorg. Med. Chem. Lett., 2017, 27, 54.
46. R. Nandini, R. Thrilokraj, U. A. Kshirsagar, R. V. Hedge, A. Ghosh, S. A. Patil, J. G. Malecki and R. B. Dateer, Facile access to 1,2-disubstituted benzimidazoles and 2,3-dihydro-1H-perimidines using a biogenically synthesized single phase d-MnO₂ NP catalyst and its dye removal study, New J. Chem., 2024, 48, 1327–1335.

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