Acceptorless, Reversible Dehydrogenation and Hydrogenation of N

Research Article pubs.acs.org/acscatalysis

Acceptorless, Reversible Dehydrogenation and Hydrogenation of N‑Heterocycles with a Cobalt Pincer Catalyst Ruibo Xu,†,‡,¶ Sumit Chakraborty,†,¶ Hongmei Yuan,† and William D. Jones*,† †

Department of Chemistry, University of Rochester, Rochester, New York 14627, United States School of Pharmacy, Huaihai Institute of Technology, Lianyungang, Jiangsu 222005, People’s Republic of China

‡

S Supporting Information *

ABSTRACT: Acceptorless, reversible dehydrogenation and hydrogenation reactions involving N-heterocycles are reported with a well-defined cobalt complex supported by an aminobis(phosphine) [PN(H)P] pincer ligand. Several N-heterocycle substrates have been evaluated under dehydrogenation and hydrogenation conditions. The cobalt-catalyzed amine dehydrogenation step, a key step in the dehydrogenation process, has been independently verified. Control studies with related cycloalkanes suggest that a direct acceptorless alkane dehydrogenation pathway is unlikely. The metal−ligand cooperativity is probed with the related [PN(Me)P] derivative of the cobalt catalyst. These results suggest a bifunctional dehydrogenation pathway and a nonbifunctional hydrogenation mechanism. KEYWORDS: acceptorless dehydrogenation, hydrogenation, cobalt catalysis, N-heterocycles, pincer ligands, H2 storage materials

A

studies, Xiao and co-workers have developed cyclometalated imino-iridium complexes as dehydrogenation−hydrogenation catalysts for a broad range of N-heterocycles.6f,h Despite the progress with these iridium-based catalysts, there is interest in the development of efficient homogeneous catalysts containing sustainable transition metals, such as iron, cobalt, and nickel, for these reactions. Our group has recently reported the first iron catalyst, supported by an aminobis(phosphine) pincer ligand (HN[(CH2)2PiPr2]2 (abbreviated as iPr [PN(H)P] ligand), for the reversible dehydrogenation/ hydrogenation of N-heterocycles.8 A wide variety of Nheterocycles, including saturated and unsaturated quinoline, imidazole, and pyridine derivatives, were successfully explored. The mechanism, highlighting the role of the metal−ligand cooperativity, has been investigated by experimental and DFT studies.9 In our continuous efforts to discover first-row transitionmetal catalysts for these challenging transformations, we focused our attention on the Cy[PN(H)P]-supported cobalt complexes (Cy: cyclohexyl) for the purpose of comparing the activity of cobalt with that of iron. Hanson and co-workers have used these cobalt complexes (preformed or generated in situ) as efficient catalysts for the dehydrogenation of alcohols and hydrogenation of olefins, aldehydes, ketones, and imines (Figure 1).10 It is noteworthy that primary amines have been used as trapping reagents in the cobalt-catalyzed dehydrogenation of primary alcohols to generate imines from the corresponding Schiff base reaction.10b Interestingly, under the catalytic conditions (at 120 °C), no products arising from the

cceptorless catalytic dehydrogenation and hydrogenation of N-heterocycles are two of the most atom-efficient ways to produce quinoline and tetrahydroquinoline derivatives that are an integral part of numerous pharmaceuticals and bioactive molecules.1 In addition, these reactions are also applicable to the field of liquid organic hydrogen storage materials2 and commercial fuel cells.3 Acceptorless dehydrogenation of Nheterocycles is a thermodynamically uphill process at ambient conditions; however, experimental and computational studies have demonstrated that the presence of the nitrogen atom in these heterocycles decreases the ΔH0 of the reaction when compared with regular cycloalkanes.4 As H2 gas is released during this process, the de/hydrogenation equilibrium can be altered by removing H2 from the system.4c Although several heterogeneous5 and few homogeneous catalysts6−8 have been reported to carry out either acceptorless dehydrogenation or hydrogenation of N-heterocycles, examples of a single metal catalyst for both the reactions are extremely rare in the literature.5h,6a,i,8 Fujita and co-workers first reported a well-defined homogeneous iridium catalyst, supported by a noninnocent 2hydroxypyridine ancillary ligand, for the dehydrogenation of tetrahydroquinoline derivatives under mild conditions.6a DFT studies have indicated a ligand-promoted hydrogen abstraction from the substrate without changing the formal oxidation state of the iridium(III) center.6c Remarkably, the same iridium complex can also catalyze the hydrogenation of unsaturated quinoline derivatives under an atmospheric pressure of H2. More recently, Fujita et al. have reported similar iridium catalysts bearing a bipyridonate ligand for the perdehydrogenation and perhydrogenation of fused bicyclic N-heterocycles that have more H2 content per molecule.6i In addition to these © 2015 American Chemical Society

Received: September 9, 2015 Published: September 15, 2015 6350

DOI: 10.1021/acscatal.5b02002 ACS Catal. 2015, 5, 6350−6354

Research Article

ACS Catalysis

Table 1. Cobalt-Catalyzed Acceptorless Dehydrogenation of N-Heterocyclesa

Figure 1. Past and current applications of the cobalt pincer catalyst (1).

dehydrogenation of the primary amine were observed. We questioned if it is possible to dehydrogenate amines using this cobalt pincer complex. Encouraged by the critical role of the [PN(H)P] ligand in the iron system8,9 and superior activities of these cobalt complexes in dehydrogenation and hydrogenation reactions,10 we became interested in investigating catalytic dehydrogenation and hydrogenation of N-heterocycles, containing a cyclic secondary amine moiety, with the [PN(H)P]-supported cobalt complexes. Herein, we report for the first time that the preformed cobalt complex, [{CyPN(H)P}Co(CH2SiMe3)]BArF4 (1), can effectively catalyze both the acceptorless dehydrogenation and hydrogenation of different N-heterocycles under relatively mild conditions. Preliminary mechanistic results indicate a metal−ligand cooperative pathway for the dehydrogenation process and a noncooperative process for the hydrogenation reaction. To determine the optimum conditions for catalysis, we studied catalytic dehydrogenation of 1,2,3,4-tetrahydroquinaldine (a) in the presence of complex 1 (5−20 mM) under various conditions (Table S-1 in the Supporting Information). Carrying out the catalytic reactions between 100 and 120 °C using relatively low-boiling solvents, such as THF and toluene, did not produce any of the desired unsaturated product. In contrast, when the same reaction mixture was heated to 150 °C in high-boiling p-xylene solvent, ∼ 83% of a was converted to form quinaldine (a′) as the sole dehydrogenation product after 4 days.11 No partially dehydrogenated species was observed during this process when the reaction was monitored by gas chromatography at intermediate times. When the concentration of the catalyst was doubled, a′ was formed in almost quantitative amounts (91%) at 150 °C. Control experiments without the catalyst did not yield any dehydrogenation product. Furthermore, the homogeneous nature of this system was indicated by the reproducible kinetic profile without an induction period (see the Supporting Information, Figure S4). We next investigated the scope of N-heterocycle substrates (100 mM) in the dehydrogenation reaction with 10 mol % of 1 (10 mM) in p-xylene at 150 °C (Table 1). Under these catalytic conditions, several N-heterocyclic compounds (a−d), including six-membered tetrahydroquinoline and five-membered 2methylindoline, were successfully dehydrogenated to produce the respective aromatic products (a′−d′) with almost quantitative GC conversions and good GC yields. 1,2,3,4Tetrahydroquinoline reacted much more slowly in the presence of 10 mol % of catalyst and afforded only 24% conversion after 4 days. In marked contrast to other N-heterocyclic substrates, dehydrogenation of 2,6-dimethylpiperidine (e) did not afford

Conditions: 1 (10 μmol, 10 mM); N-heterocyclic substrate (0.1 mmol, 100 mM); p-xylene (1 mL); heated at 150 °C in a 500 mL, round-bottom ampule fitted with a Kontes valve. bConversions were calculated from the relative peak area integrations of the reactant and product in the GC spectra. cYields were determined by GC using dodecane as the internal standard. d20 mol % of 1 was used. eWith 10 mol % of 1, 74% conversion was observed after 4 days. a

any of the desired product under these conditions. Hazari and co-workers have recently reported accelerated rate effects of adding a Lewis acid catalyst in the dehydrogenation of formic acid and methanol.12 Inspired by these studies, we attempted to carry out the dehydrogenation of e in the presence of Lewis acids, such as LiBF4 and B(C6F5)3. Unfortunately, these additives had no effect on this reaction, and no dehydrogenation activity was observed. In addition, a much less bulky substrate piperidine could not be dehydrogenated under these conditions. In comparison, the related iPr[PN(H)P] iron complex catalyzes the complete dehydrogenation of 2,6-dimethylpiperidine to afford 2,6-lutidine under similar conditions.8 Catalytic dehydrogenation of 1,2,3,4-tetrahydroquinoxaline (f), containing two amine moieties in the same molecule, proceeded smoothly to yield the desired quinoxaline derivative as the sole product. It is interesting to note that the formation of the quinoline moieties does not inhibit the catalysis by binding to the cobalt center through the basic N atoms. Although unclear at this point, the steric and electronic properties of the Cy [PN(H)P] ligand might play a crucial role in preventing catalyst inhibition by substrate or product coordination. 6351

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Table 2. Hydrogenation of Unsaturated N-Heterocyclesa

To confirm the identity of the released gas from the dehydrogenation reaction, the volatiles were vacuum-transferred from the reaction vessel to a sealed J. Young NMR tube containing a chilled solution of C6D6. Recording the 1H NMR spectrum of the resulting solution showed a singlet resonance at δ4.47 that is characteristic for dihydrogen. In addition, the released H2 gas was also detected by gas chromatography (see the Supporting Information, Figure S2). To test the reusability of the catalyst, after the first catalytic run with substrate a (with 20 mol % 1), a fresh batch of substrate was introduced into the system, and the reaction was carried out for four more days at 150 °C. In this second run, 84% of a was converted to a′, indicating that the catalyst decomposition is minimal. Once the protocol for the cobalt-catalyzed dehydrogenation of N-heterocycles was demonstrated, we became interested in carrying out the microscopic reverse of the dehydrogenation process with the same cobalt catalyst 1. As mentioned earlier, it is rare to find a single transition metal catalyst that can perform both dehydrogenation and hydrogenation reactions involving N-heterocycles.8,13 We performed catalytic hydrogenation of quinaldine (a′) under various conditions (see Table S2 in the Supporting Information). We observed that a′ could be quantitatively converted to a in the presence of 5 or 10 mol % of 1, 10−20 atm of H2 pressure at 120 °C in THF. Remarkably, almost quantitative (90%) hydrogenation of quinaldine b′ could also be achieved with a H2 pressure as low as 5 atm. Having established the best hydrogenation conditions (5 mol % of 1, 10 atm H2), we next planned to expand the substrate scope of this reaction (Table 2). For quinoline derivatives (entries 1, 2, and 6), quantitative conversions were observed in 2 days to produce the respective products (entries 1, 2, 6). In all of these quinoline substrates, the aromatic phenyl ring remained intact after the reaction. Surprisingly, under optimum catalytic conditions, only 11% of isoquinoline (c′) was converted to the corresponding saturated compound. Doubling both the catalyst concentration and the H2 pressure increased the conversion to 56% (entry 3). In the case of the 2methylindole (entry 4), a much lower conversion (24%) was observed, as well. Furthermore, attempts to hydrogenate 2,6lutidine (e′, entry 5) proved unsuccessful, even at a much higher temperature (150 °C) and with a higher pressure of H2 (20 atm). Recently, Fujita and co-workers have reported perhydrogenation of fused bicyclic N-heterocycles with an iridium bipyridinone complex with a high H2 pressure (70 atm).6i The fully hydrogenated bicyclic product carries more hydrogen per molecule and therefore is an attractive hydrogen storage material. Inspired by this finding, we planned to test perhydrogenation of 1,5-naphthyridine (h′) with cobalt catalyst 1. When the reaction was performed in the presence of 20 atm of H2, h′ was almost quantitatively converted (98%), and h was observed as the only hydrogenation product. One of the pyridine rings remained intact in this process, and this observation is also consistent with the observed inactivity of e′ under this condition. Experimental support for the first amine dehydrogenation step to release the first equivalent of dihydrogen comes from the successful dehydrogenation reaction observed for f by complex 1 under standard catalytic conditions (Figure 2, eq 1). Monitoring this reaction periodically by gas chromatography and comparing the relative rates of dehydrogenation with 1,2,3,4-tetrahydroquinoline indicates that the rate of the first

Conditions: 1 (10 μmol, 10 mM), substrate (0.2 mmol, 200 mM), 2 mL THF, pH2 = 10 atm. bConversions were calculated from the relative peak area integrations in the GC spectra. cYields were determined by GC using dodecane as the internal standard. d10 mol %, 20 atm H2. e 150 °C. a

Figure 2. Relative Rates of Dehydrogenation (with 10 mol % 1).

amine-dehydrogenation step is comparable and that it is likely to be slower than the second dehydrogenation step (Figure 2), 6352

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oxidized N-heterocycles. Replacement of the N−H moiety in the pincer ligand in 1 with N-Me inhibited the dehydrogenation activity but retained its hydrogenation activity. These results differ from what has been observed in the dehydrogenation−hydrogenation reactions involving alcohols and ketones. Future efforts will be focused on pursuing a detailed mechanistic investigation to rationalize these differences, and these results will be reported in the future.

since no partially dehydrogenated product was observed at any given time during catalysis. To release the second equivalent of H2 from the substrate, two C−H bonds need to be broken. This could happen by two different pathways: (a) a direct alkane dehydrogenation14 by cobalt from the partially oxidized substrate or (b) isomerization of the initially formed CN to a CC, followed by a second dehydrogenation from the secondary amine fragment.6e To test this hypothesis, we carried out dehydrogenation reactions of the following substrates with catalyst 1: (i) 1,2,3,4-tetrahydronaphthalene and (ii) 1,2-dihydronaphthalene. For these two substrates (without any N atom), no dehydrogenation activity was observed, suggesting the direct alkane dehydrogenation pathway is unlikely (eq 2).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.5b02002. Experimental procedures and product characterization data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected].

To elucidate the involvement of the N−H moiety on the pincer ligand in the catalysis, the reactivities of 1 and [Cy{PN(Me)P}Co(CH2SiMe3)]BArF4 (1-Me)10c were compared (Scheme 1). Hanson and co-workers have reported

Author Contributions ¶

R.X. and S.C. contributed equally.

Notes

The authors declare no competing financial interest.

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Scheme 1. Probing Metal−Ligand Cooperativity

ACKNOWLEDGMENTS This work was funded by the Center for Electrocatalysis, Transport Phenomena, and Materials (CETM) for Innovative Energy Storage, an EFRC funded by the U.S. DOE (Award DESC0001055); the ESD NYSTAR program; and in part, by NSF under the CCI Center for Enabling New Technologies through Catalysis (CENTC), CHE-1205189.

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REFERENCES

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that complex 1-Me displayed catalytic activity similar to that of 1 in the dehydrogenation of 1-phenylethanol,10c but the same methyl derivative was found to be an inactive catalyst for the hydrogenation of ketones (with 1 atm H2 pressure). In stark contrast, we observed that although the dehydrogenation of 1,2,3,4-tetrahydroquinaldine was completely inhibited in the presence of the 1-Me catalyst, hydrogenation of quinaldine proceeded smoothly (∼80% conversion) to produce the desired product under standard catalytic conditions (Scheme 1). The completely opposite reactivity of 1-Me catalyst in the amine dehydrogenation reaction points toward an energetically or a mechanistically different scenario from the alcohol/ketone case. It is also possible that the differences in the catalytic conditions, especially the H2 pressure, between the two systems allow for the variation in the mechanisms. Nevertheless, results shown in Scheme 1 suggest that the cobalt catalyst 1 dehydrogenates N-heterocycles in a cooperative fashion involving the N−H moiety on the pincer ligand. In contrast, the hydrogenation reaction can proceed without the involvement of the N−H group. In summary, we have demonstrated reversible dehydrogenation/hydrogenation of N-heterocycles with an inexpensive and earth-abundant molecular cobalt pincer catalyst in the absence of an acceptor. Respective products from both dehydrogenation and hydrogenation reactions were formed with high conversions and yields. Substrate-driven mechanistic studies support the initial amine-dehydrogenation step and argue against a direct alkane dehydrogenation step from the partially 6353

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