Dehydrogenative Oxidation of Cyclic Amines on a Diruthenium

Communication pubs.acs.org/Organometallics

Dehydrogenative Oxidation of Cyclic Amines on a Diruthenium Complex Ryuichi Shimogawa,† Ryosuke Fujita,† Toshiro Takao,*,†,‡ and Hiroharu Suzuki† †

Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan ‡ JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan S Supporting Information *

ABSTRACT: The dehydrogenative oxidation of cyclic amines catalyzed by a diruthenium complex and mechanistic studies are described. Cyclic amines and water reacted in the presence of Cp‡Ru(μ-H)4RuCp‡ (1) (Cp‡ = 1,2,4tri-tert-butylcyclopentadienyl) to afford lactams accompanied by elimination of the hydrogen gas. The reaction of hexamethylenimine with 1 at 160 °C afforded Cp‡Ru(μ-H)2(μ-C6H11N)RuCp‡ (2), having a novel μ-cyclic imine ligand through N−H and C−H bond cleavages. Further C−H bond cleavage of 2 proceeded at 180 °C to afford Cp‡Ru(μ-H)(μ-η2:η2C6H10N)RuCp‡ (4), having a perpendicularly coordinated imidoyl ligand. Complex 4 readily reacted with water and liberated ε-caprolactam. The cooperative interaction of the two ruthenium atoms leading to N−H and double C−H bond cleavages was the key to the dehydrogenative oxidation of cyclic amines.

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ehydrogenative coupling reactions of sp3 C−H bonds with E−H bonds are considered among the most atomeconomical reactions. Despite the challenging C−H functionalization owing to the large dissociation energy of the C−H bond, many approaches have been developed, including chelating type directing group assisted C−H functionalization1 and a radical mechanism.2 Lactams are widely used as precursors for polymers and pharmaceuticals and are commonly synthesized by cyclization of amino acids and Beckman rearrangement.3 Direct oxidation of cyclic amines at the α position would provide an alternative simplified method; however, synthesis involving direct oxidation is still limited.4 Recently, Milstein and co-workers established a unique lactam formation from cyclic amines and H2O via sp3 C−H bond activation by an acridine-based ruthenium pincer complex.5 Multimetallic systems have been intensively studied and have shown high reactivity toward the activation of inert bonds through the “multimetallic interaction”.6 In this regard, heterocyclic compounds should be suitable candidates to allow efficient sp3 C−H bond activation at the α position at a multimetallic site. It has been shown that trinuclear clusters reacted with cyclic amines to yield μ3-η2(∥)-imidoyl complexes as a consequence of both sp3 C−H and N−H bond scissions.7 However, the reactivity of μ3-imidoyl complexes has been scarcely investigated.8 It is well-known that free imine undergoes nucleophilic attack at the electrophilic carbon atom. Thus, it is expected that such imine-like species at a multimetallic site will be susceptible to nucleophilic attack although such reactivity has never been explored. In this © XXXX American Chemical Society

communication, we demonstrate the catalytic lactam formation from cyclic amines and H 2 O using the diruthenium tetrahydrido complex Cp‡Ru(μ-H)4RuCp‡ (1) (Cp‡ = 1,2,4tri-tert-butylcyclopentadienyl).9 The neighboring metal centers of 1 are expected to operate both N−H and sp3 C−H bond scissions efficiently. In addition, the bulky Cp‡ ligands of 1 can stabilize a series of unsaturated diruthenium species and hence promote hydrogen elimination from the dinuclear site, which causes feasible incorporation of H2O leading to oxygenation of a μ-imidoyl ligand. We first attempted the dehydrogenative oxidation of pyrrolidine in the presence of water using 1 as a catalyst. The reaction of 1 with 1000 equiv of pyrrolidine and 1000 equiv of water at 180 °C for 24 h afforded 2-pyrrolidone with a turnover number (TON) of 115. The reaction rate accelerated with an increase in temperature, and a dramatic increase in activity was observed above 160 °C. The yield of 2-pyrrolidone increased with an increase in the amount of water. However, too much water caused a decrease in the yield. This is likely owing to the low solubility of 1 toward the polar solvent. Addition of H2 was effective for decreasing the induction period. As mentioned below, dihydrogen plays an important role for the regeneration of active species in the catalytic cycle. The conditions were further optimized as follows: 180 °C, under atmospheric H2, and pyrrolidine/water = 1/2 molar ratio (Table 1). Under these conditions, conversion of pyrrolidine reached 29% and 2-pyrrolidone was obtained in 23% yield Received: March 29, 2017

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DOI: 10.1021/acs.organomet.7b00231 Organometallics XXXX, XXX, XXX−XXX

Communication

Organometallics Table 1. Dehydrogenative Coupling of Cyclic Aminesf

and the structure was unambiguously determined by X-ray diffraction (XRD) studies, as depicted in Figure 1. The

Figure 1. Molecular structure of 2 with thermal ellipsoids set at 30% probability. Hydrogen atoms of Cp‡ and imine moieties are omitted for clarity.

structure clearly demonstrates that both N−H and C−H bonds of hexamethylenimine are broken, and this is likely due to the cooperative interaction of the neighboring Ru centers of 1. Complex 2 also catalyzed the reaction of pyrrolidine with water. This fact strongly implies the contribution of the μ-cyclic imine complex to the catalytic cycle. The cyclic imine moiety of 2 adopts a rare μ-η2 coordination mode at the dinuclear site, like the more familiar μ-vinyl ligands. To the best of our knowledge, this is the first X-ray structure of a μ-η2-imine ligand, and such a coordination mode of an imine has only been reported for [{(dippe)Rh}2(μ-RN CPhH)(μ-H)]+ (R = CH3, C6H5) by Fryzuk and co-workers.12 Similarly to Fryzuk’s complex, the μ-imine ligand in 2 undergoes oscillation between the two Ru centers, as evidenced by variable-temperature 1H NMR measurements (Figure S-7 in the Supporting Information). The reaction of 2 with H2O in t-BuOH resulted in the formation of the diruthenium bis(μ-hydroxo) complex {Cp‡Ru(μ-OH)}2 (3) accompanied by the liberation of ε-caprolactam (eq 2). It is noteworthy that 3 adopts a dinuclear structure due

a

Determined by GC analysis using biphenyl as an external standard. Isolated yield. cUnder an Ar atmosphere. dCatalyst Cp*2Ru2H4. e Conversions were not determined due to the low yield. fStandard conditions: 1, substrate/water/catalyst = 1000/2000/1, H2 (1 atm), 180 °C, 72 h. b

(TON = 226). Although we could not identify the byproduct, it may be formed via the reaction of cyclic amine with a hydrolysis product of lactam. Milstein and co-workers elucidated the major byproduct of dehydrogenative oxidation of pyrrolidine as 4-(1-pyrrolidynyl)butanoic acid.5 It is noteworthy that the Cp* analogue, Cp*Ru(μ-H)4RuCp*,10 also catalyzes the lactam formation, but less selectively than 1 (Table 1, entry 3). The sterically demanding reaction site arising from Cp‡ ligands seems to suppress side reactions. Although TONs significantly decreased in comparison to that observed in the reaction with pyrrolidine, piperidine and hexamethylenimine also reacted to afford corresponding lactams (Table 1, entries 4 and 5). These results indicate that the activity is highly influenced by the steric bulk of the substrate. Despite the six-membered structure, the corresponding lactam was not formed by the reaction of 1 with morpholine (Table 1, entry 6). We speculate that the formation of catalytically inactive species as a consequence of oxygen atom directed reactions is responsible for this failed reaction. We have previously shown that 1 reacts with tetrahydrofuran to yield a μ-oxycarbene complex.11 The stoichiometric reaction of 1 with cyclic amines was then investigated to elucidate the mechanism. Complex 1 reacted with hexamethylenimine at 160 °C to afford the μ-cyclic imine complex 2 in 71% yield (eq 1). Complex 2 was fully characterized by NMR spectroscopy and elemental analysis,

to the bulk of the Cp‡ ligands, unlike the well-known tetrameric structure of the Cp* analogue.13 The molecular structure of 3 B

DOI: 10.1021/acs.organomet.7b00231 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

coordination mode of the imidoyl ligand changed from perpendicular to parallel with respect to the Ru−Ru vector. The parallel coordination mode of the imidoyl moiety was unambiguously confirmed by XRD, as shown in Figure 3.

was confirmed by XRD (Figure S-4 in the Supporting Information). During the formation of 3, the solution initially turned from purple to brown and then to red-purple, which is the characteristic color of 3. This color change implies that an intermediate is formed at the beginning of the hydrolysis. Thus, thermolysis of 2 in the absence of H2O was investigated. Heating a hexane solution of 2 at 180 °C resulted in a color change to brown. Instantaneous freezing of the reaction mixture with a liquid-nitrogen bath allowed the isolation of μ-imidoyl complex 4 (eq 3). The structure of 4, determined by

Figure 3. Molecular structure of 5 with thermal ellipsoids set at 30% probability. Hydrogen atoms of Cp‡, imidoyl, and trimethylphosphine moieties are omitted for clarity.

XRD, clearly shows that the imine C−H bond is broken and the resulting imidoyl ligand adopts a μ-η2:η2 coordination mode at the Ru2 site (Figure 2). While we have previously reported

Hydrolysis of 4 in t-BuOH gave 3 in 74% yield and εcaprolactam in 58% yield. This fact strongly suggests that hydrolysis of the μ-imine ligand in 2 occurs via the formation of μ-imidoyl complex 4, and its highly unsaturated nature seems to promote incorporation of H2O into the Ru2 site, as seen in the ligation of PMe3. A plausible mechanism for the dehydrogenative oxidation of cyclic amines is shown in Scheme 1. Cooperative interaction of Scheme 1. Proposed Reaction Mechanism for the Dehydrogenative Oxidation Reaction of Hexamethyleneimine

Figure 2. Molecular structure of 4 with thermal ellipsoids set at 30% probability. Hydrogen atoms of Cp‡ and imidoyl moieties are omitted for clarity.

the synthesis of triruthenium complexes containing a μ3imidoyl ligand perpendicularly coordinated to one of the Ru− Ru bonds,14 little is known about the dinuclear complexes to date.15 Formation of 4 was rationalized by hydrogen elimination form the diruthenium core via a C−H bond scission at the μ-η2imine moiety of 2. Consequently, valence electrons of 4 decreased to 30 electrons from 32 electrons in 2. In fact, 4 is highly reactive and treatment of 4 with atmospheric H2 at ambient temperature resulted in the immediate regeneration of 2. The sterically demanding Cp‡ ligands seem to be responsible for the stabilization of such unsaturated species. Complex 4 also reacted with PMe3 to yield phosphine adduct 5 (eq 4). Alongside the incorporation of PMe 3 , the

the diruthenium center with the cyclic amine renders C−H and N−H bond cleavage, leading to the formation of 2. Subsequent C−H bond activation at the imine carbon affords μ-imidoyl complex 4, which allows incorporation of H2O to form parallel imidoyl intermediate A. Oxidative addition of an O−H bond followed by reductive C−O bond formation affords intermediate B containing a 7-hydroxy-3,4,5,6-tetrahydro-2H-azepin ligand. Intermediate B reacts further with H2O to yield 3 accompanied by the elimination of the lactim, which undergoes tautomerization to the lactam. C

DOI: 10.1021/acs.organomet.7b00231 Organometallics XXXX, XXX, XXX−XXX

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(3) Ogliaruso, M. A.; Wolfe, J. F.; Patai, S.; Rappoport, Z. In Synthesis of lactones and lactams; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, U.K., 1993. (4) (a) Moriarty, R. M.; Vaid, R. K.; Duncan, M. P.; Ochiai, M.; Inenaga, M.; Nagao, Y. Tetrahedron Lett. 1988, 29, 6913−6916. (b) Tsuboi, S.; Ishii, N.; Sakai, T.; Tari, I.; Utaka, M. Bull. Chem. Soc. Jpn. 1990, 63, 1888−1893. (c) Chandrakala, M.; Murthy, K. V. V. S. B. S. R.; Kulkami, S. J.; Raghavan, K. V. Indian J. Chem. 2000, 39B, 71− 73. (d) Tada, N.; Miyamoto, K.; Ochiai, M. Chem. Pharm. Bull. 2004, 52, 1143−1144. (e) Dairo, T. O.; Nelson, N. C.; Slowing, I. I.; Angelici, R. J.; Woo, L. K. Catal. Lett. 2016, 146, 2278−2291. (f) Jin, X.; Kataoka, K.; Yatabe, T.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2016, 55, 7212−7217. (5) (a) Khusnutdinova, J. R.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 2014, 136, 2998−3001. (b) Gellrich, U.; Khusnutdinova, J. R.; Leitus, G. M.; Milstein, D. J. Am. Chem. Soc. 2015, 137, 4851−4859. (6) For example: (a) Akagi, F.; Matsuo, T.; Kawaguchi, H. Angew. Chem., Int. Ed. 2007, 46, 8778−8781. (b) Fryzuk, M. D. Acc. Chem. Res. 2009, 42, 127−133. (c) Takao, T.; Suzuki, H. Coord. Chem. Rev. 2012, 256, 695−708. (d) Shima, T.; Hu, S.; Luo, G.; Kang, X.; Luo, Y.; Hou, Z. Science 2013, 340, 1549−1552. (e) Shimogawa, R.; Takao, T.; Konishi, G.; Suzuki, H. Organometallics 2014, 33, 5066−5069. (f) Hu, S.; Shima, T.; Hou, Z. Nature 2014, 512, 413−415. (g) Takao, T.; Suzuki, H. Bull. Chem. Soc. Jpn. 2014, 87, 443−458. (7) (a) Süss-Fink, G.; Jenke, T.; Heitz, H.; Pellinghelli, M. A.; Tiripicchio, A. J. J. Organomet. Chem. 1989, 379, 311−323. (b) Day, M. W.; Hajela, S.; Kabir, S. E.; Irving, M.; McPhillips, T.; Wolf, E.; Hardcastle, K. I.; Rosenberg, E.; Milone, L.; Gobetto, R.; Osella, D. Organometallics 1991, 10, 2743−2751. (c) Adams, R. D.; Chen, G. Organometallics 1993, 12, 2070−2077. (d) Day, M.; Espitia, D.; Hardcastle, K. I.; Kabir, S. E.; McPhillips, T.; Rosenberg, E.; Gobetto, R.; Milone, L.; Osella, D. Organometallics 1993, 12, 2309−2324. (e) Cifuentes, M. P.; Humphrey, M. G.; Skelton, B. W.; White, A. H. J. J. Organomet. Chem. 1993, 458, 211−218. (f) Kabir, S. E.; Rosenberg, E.; Day, M.; Hardcastle, K. I.; Irving, M. J. Cluster Sci. 1994, 5, 481− 503. (8) (a) Kabir, S. E.; Rosenberg, E.; Day, M.; Hardcastle, K. I. Organometallics 1994, 13, 4437−4447. (b) Rosenberg, E.; Milone, L.; Gobetto, R.; Osella, D.; Hardcastle, K.; Hajela, S.; Moizeau, K.; Day, M.; Wolf, E.; Espitia, D. Organometallics 1997, 16, 2665−2673. (c) Kabir, S. E.; Rosenberg, E.; Milone, L.; Gobetto, R.; Osella, D.; Ravera, M.; McPhillips, T.; Day, M. W.; Carlot, D.; Hajela, S.; Wolf, E.; Hardcastle, K. Organometallics 1997, 16, 2674−2681. (9) (a) Yanagi, T.; Suzuki, H.; Oishi, M. Chem. Lett. 2013, 42, 1403− 1405. (b) Shimogawa, R.; Takao, T.; Suzuki, H. Organometallics 2014, 33, 289−301. (c) Shimogawa, R.; Takao, T.; Suzuki, H. J. Organomet. Chem. 2016, 801, 6−9. (10) Suzuki, H.; Omori, H.; Lee, D. H.; Yoshida, Y.; Fukushima, M.; Tanaka, M.; Moro-oka, Y. Organometallics 1994, 13, 1129−1146. (11) Shimogawa, R.; Konishi, G.; Takao, T.; Suzuki, H. Organometallics 2016, 35, 1446−1457. (12) Fryzuk, M. D.; Piers, W. E. Organometallics 1990, 9, 986−998. (13) Suzuki, H.; Kakigano, T.; Igarashi, M.; Usui, A.; Noda, K.; Oshima, M.; Tanaka, M.; Moro-oka, Y. Chem. Lett. 1993, 22, 1707− 1710. (14) (a) Takao, T.; Kawashima, T.; Matsubara, K.; Suzuki, H. Organometallics 2005, 24, 3371−3374. (b) Kawashima, T.; Takao, T.; Suzuki, H. Angew. Chem., Int. Ed. 2006, 45, 485−488. (c) Kanda, H.; Kawashima, T.; Takao, T.; Suzuki, H. Organometallics 2012, 31, 1917− 1926. (15) (a) Feng, Q.; Ferrer, M.; Green, M. L. H.; McGowan, P. C.; Mountford, P.; Mtetwa, V. S. B. J. Chem. Soc., Chem. Commun. 1991, 552−554. (b) Tayebani, M.; Gambarotta, S.; Yap, G. Organometallics 1998, 17, 3639−3641. (c) Alvarez, M. A.; García, M. E.; García-Vivó, D.; Ruiz, M. A.; Vega, M. F. Organometallics 2013, 32, 4543−4555.

Regeneration of 1 was achieved by the reaction of bis(μhydroxo) complex 3 with atmospheric dihydrogen, and 1 was obtained in 69% yield. Since 1 was not regenerated smoothly in the catalysis conducted under an Ar atmosphere, accumulation of H2 is required for the smooth turnover of the catalytic cycle, which might explain why the addition of H2 shortened the induction period. In conclusion, a catalytic dehydrogenative oxidation of cyclic amines was achieved using a diruthenium complex. The stoichiometric reaction using a seven-membered cyclic amine and water revealed that the perpendicularly coordinated imidoyl complex generated by the N−H and double C−H bond cleavage was a key intermediate for the formation of the lactam. Some side reactions were observed for the reactions with five- and six-membered cyclic amines, and further details of the reaction mechanisms will be reported in the future. We believe that the double C−H bond activation at the α position of the heteroatom using cluster compounds will lead to new series of direct functionalization methods.

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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/acs.organomet.7b00231. Experimental details, crystal data and results of XRD studies of 2−5, VT-1H NMR spectrum of 2, and NMR spectra of 2−5 (PDF) Accession Codes

CCDC 1540584−1540587 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail for T.T.: [email protected]. ORCID

Ryuichi Shimogawa: 0000-0002-6507-1876 Toshiro Takao: 0000-0002-5393-112X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by JST ACT-C Grant Number JPMJCR12YA, Japan. This work was also supported by a Grant-in-Aid for JSPS Fellows grant number 26009727. R.S. thanks the JSPS Research Fellowship for Young Scientists for financial support.

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REFERENCES

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DOI: 10.1021/acs.organomet.7b00231 Organometallics XXXX, XXX, XXX−XXX