Nickel(II)-2-amino-4-alkoxy-1,3,5-triazapentadienate complexes as catalysts for Heck and Henry reactions

Abstract

Nickel(II)-triazapentadienate complexes, [Ni(tap)₂], are synthesized and found to act as catalysts in the Heck reaction of deactivated aryl halides. The use of room-temperature ionic liquids instead of organic solvents allows easy separation of the catalyst from the products and substrates. The synthesized complexes also catalyse the Henry reaction of benzaldehydes with nitroethane, at 25 °C, leading to the corresponding nitroalkanols with diastereoselectivity in favour of the anti isomer.

---

Introduction

Despite the high potential of 1,3,5-triazapentadienes (tap) as N,N-chelating ligands in coordination chemistry¹ (Scheme 1) and the number of available synthetic procedures,^1–3 the reported applications of metal-tap complexes are rather limited.^4,5 Aiming to broaden the possible applications of such a type of metal complexes, the catalytic activity of nickel(II)-tap compounds in the Heck and Henry C–C coupling reactions was tested in this work.

Scheme 1 Schematic representation of triazapentadiene ligands (a and b) and metal-tap complexes (c and d); R = alkyl, aryl, alkoxy, amine; X and Y are auxiliary ligands.

The Heck reaction is one of the most useful transformations in organic chemistry, based on Csp₂–Csp₂ coupling of a wide range of aryl halides (and pseudo halides, i.e. triflates) with olefins, traditionally using palladium catalysts under basic conditions in organic solvents.⁶

The mechanism involves the oxidative addition of the aryl halide to the palladium center,^6–9 which depends on the carbon–halogen bond strength and is hampered by electron rich aryl halides (the so called deactivated aryl halides).⁶ Current developments have focused on (i) the design of new ligands, such as mono- and polydentate phosphines, cyclometalated phosphines, N,N-chelating ligands, etc.⁶ that can enhance the activity of the palladium based catalytic systems towards the transformation of aryl chlorides and/or deactivated aryl halides, (ii) the search of regioselective catalytic systems,^10–12 and (iii) the search of new low-cost metal catalysts for replacement of the palladium ones.¹³ Following these trends, and taking also into account the potential of nickel compounds in cross-coupling reactions, particularly in Heck reaction,^13–15 we have now evaluated the activity of a catalytic system based on nickel(II)-2-amino-4-alkoxy-1,3,5-triazapentadienato complexes, using triphenylphosphine as reducing agent. The reactions were performed in room-temperature ionic liquids,^16,17 that have temperature dependent miscibility with other solvents, but readily dissolving many transition metal catalysts.¹⁷

The Henry reaction is a Csp₃–Csp₂ coupling reaction between a nitroalkane and a carbonyl compound giving β-nitroalcohols that can be further converted into various important organic products.^18–20 In spite of the progress of the method, good enantio- and diastereoselectivity is rarely achieved.²¹ Our group has previously investigated⁵ the activity of a zinc(II)-tap as catalyst for this reaction, and now we report the extension to nickel(II)-tap catalysts.

Results and discussion

The synthesis of novel nickel(II)-2-amino-4-alkoxy-1,3,5-triazapentadienates can be performed through a template low yield (9–11%, based on the metal salt) and time consuming (72 h) reaction of an alcohol with cyanoguanidine in the presence of nickel(II) ion (Scheme 2, route B) (see ESI†). However, a direct reaction of nickel hydroxide and corresponding tap salts (NH=C(OCH₃)NHC(NH₃)=NH)(CH₃COO) (3) and (NH=C(OCH₂CH₃)NHC(NH₃)=NH)(NO₃) (4) that can be liberated as stable salts by the reaction of the corresponding copper(II)-tap complexes (prepared via template procedure with yields of 82 and 96% for 1 and 2, respectively)⁴ with acetylacetone (Hacac), is more efficient (Scheme 2, route A) (see ESI†).⁴

Scheme 2 Synthetic procedures towards nickel(II)-tap complexes.

In this work we have followed the latter route and the new compounds [Ni{N=C(OCH₃)NHC(NH₂)=NH}₂] (5) or [Ni{N=C(OCH₂CH₃)NHC(NH₂)=NH}₂] (6) were obtained by reaction of nickel(II) hydroxide with triazapentadiene salts (3 or 4) in aqueous solution. They were isolated in good yields (87–81%) as light orange precipitates which were recrystallized from acetone to afford suitable crystals for X-ray diffraction analysis. The compounds were also characterized by IR, ESI⁺-MS and elemental analyses (see ESI†). The IR spectra of 5 and 6 contain typical ν (N–H) stretches at ca. 3330 cm⁻¹, ν (C=N) at ca. 1620 cm⁻¹, and δ (N–H) at ca. 1580 cm⁻¹. The ESI⁺-MS spectra show signals of the [M + H]⁺ molecular cations with the characteristic isotopic distribution at m/z ca. 289 (5) and ca. 317 (6). The molecular structures²² of 5 and 6 (Fig. 1) consist of mononuclear fragments with the 1,3,5-triazapentadienato ligands acting as N,N-chelators. Each Ni(II) cation exhibits a square-planar coordination geometry. The Ni–N bond lengths range from 1.847(2) to 1.859(2) Å (Table S4†) and the minimum Ni⋯Ni distance assume values of 6.3321 (in 5) and 6.5021 (in 6).

Fig. 1 Molecular structures of (a) [Ni{N=C(OCH₃)NHC(NH₂)=NH}₂] (5) and (b) [Ni{N=C(OCH₂CH₃)NHC(NH₂)=NH}₂] (6). Ellipsoids are drawn at 30% probability level. Symmetry operation to generate equivalent atoms: (i) 1 − x, 2 − y, 2 − z (5); 1/2 − x, 1/2 − y, 1 − z (6).

Compounds 5 and 6 were tested as catalysts for the Heck reaction where a deactivated aryl halide (bromoanisole or iodoanisole) and the electron-poor olefin butyl acrylate were chosen as substrates (Scheme 3). Triphenylphosphine was used as reducing agent, and the thermally stable room-temperature ionic liquids (ILs) 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF₆], or 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [bmim][NTf₂], as solvents (Scheme S1†).¹⁶ The reactions were performed in the presence of a base, in a sealed reactor and under microwave irradiation, typically at 180 °C (for the reaction conditions see ESI†).²³

Scheme 3 Heck reaction catalyzed by nickel(II)-tap complexes.²³

The use of the IL allowed an easy separation of the product from the catalyst, since at high temperature the IL dissolves all components of the reaction mixture, but at room temperature the substrates and products form a second phase (Fig. 2), apart from that, the hydrophobic nature of the ILs allowed to use water for the extraction of the salt byproducts (Fig. S1†).¹⁷ The ILs played the role of solvents, without catalytic activity, since no products were formed without the presence of the complexes (see ESI, Table S1,† runs 1–4).

Fig. 2 Biphasic medium generated by the room-temperature ionic liquid.

The presence of triphenylphosphine a reducing agent had an important effect in accord with the involvement of the Ni⁰/Ni^II redox pair in the step of oxidative addition of the aryl halide,^7,9 (Fig. 3a; Table S1,† runs 7–11).

Fig. 3 Impact of the reaction conditions on the product yield for the Heck reaction between bromoanisole and butyl acrylate, catalyzed by 5 (see ESI, Table S1†).²³

The nature of the base has significant impact on the productivity of the catalytic system, thus Et₃N exhibits higher promoting effect than NaHCO₃ and/or CsCO₃ (Fig. 3b; Table S1,† runs 11, 18, 19). This result can be devoted to the different solubilities of the chosen bases in corresponding IL. However, it can be caused by the possible involvement of the amine in coordination to the metal center that facilitates reductive elimination from Ni^II–hydride complex and catalyst regeneration,⁷ which is known to be hampered in nickel catalyzed Heck reaction.^7,11

A temperature rise from 130 to 180 °C led to an increase of the yield from 7.3 up to 10%, after 1.5 h reaction time for catalyst 5, but a further increase to 230 °C was adverse (Fig. 3c, Table S1,† runs 15, 11, 16), probably as a result of the catalyst and/or phosphine degradation.²⁴ The increase of the reaction time up to 3 h resulted in a gradual yield increase to 19%; a longer reaction time caused an yield drop to 12% (Fig. 3d, Table S1,† runs 13, 14), explainable by product degradation.

Under the optimal experimental conditions with [bmim][PF₆] as solvent, triethylamine as the base, 0.08 mmol of PPh₃, 180 °C and 3 h reaction time, the activity of complex 6 is much lower than that of 5, with only 1% of product yield (Table S1,† run 22). This may conceivably be associated with the longer length of the alkoxy substituent and/or the hampering of Ni reduction due to specific IL–solute interaction.²⁵ The use of [bmim][NTf₂] as solvent did not change the yield significantly in the case of 6 (Table S1,† run 26) but led to a marked yield drop to 2.5% with 5 (Table S1,† run 24).

Recycling studies performed for 5 showed that the activity decreased rapidly, reflecting the degradation of the catalyst. Thus, in the case of iodoanisole the product yield of 20% for the first run dropped to 13% for the second run, and to 4% for the third one (Table S2,† runs 1–3). A similar behaviour was observed for the substrate bromoanisole (Table S2,† runs 4–6).

It is worthwhile to mention that overall efficiency of the nickel catalytic system is comparable with those known in literature.¹⁴ For instance, the use of nickel bis-diimidazolylidine complex as catalyst for the reaction between bromoanisole and butyl acrylate leads to the product yield of 56% (reaction time 2 days),^14a butyl cinnamate was obtained with yield of 66% by the reaction between bromobenzene and butyl acrylate in the presence of bis(imidazolin-2-ylidine) nickel complex in 48 h,^14b use of iodobenzene and methyl acrylate as substrates allows to obtain methyl cinnamate with yield of 73%, in 16 h, using nickel acetate as pre-catalyst in N-methylpyrrolidone.^14c However, it is lower than that of palladium based catalytic systems.^6b

The catalytic studies of the nickel(II)-tap complexes 5 and 6 in the nitroaldol (Henry) reaction^26–30 between an aromatic aldehyde and nitroethane to the corresponding β-nitroalkanol (Scheme 4; Fig. 4; see ESI, Table S3†), were performed in methanol at 25 °C.³¹ The products of the catalytic reaction are mixtures of the corresponding β-nitroalkanol diastereoisomers (anti and syn forms), according to ¹H NMR analysis. The stereochemical control of the two newly generated carbon centres is difficult, in particular due to the easy epimerization of the nitro-substituent on the carbon chain²⁰ and generally is not achieved, as in the current work.

Scheme 4 Henry reaction catalyzed by nickel(II)-tap complexes.³¹

Fig. 4 Catalytic activity of complexes 5 and 6 in Henry reaction (see ESI, Table S3†).³¹

Product yields are high for the reaction of benzaldehyde or p-nitrobenzaldehyde after 24 h (e.g., 100% yield in the former case, using 6 as catalyst; Fig. 4f; Table S3,† run 2).

Diastereoselectivity favors the anti isomer. Nevertheless, it is not high (anti/syn molar ratios in the 58 : 48–79 : 21 range, Table S3†), but can be improved for lower reaction time (Fig. 4g and j, Table S3,† runs 3 or 8) although with an yield decrease. No significant nitroaldol reaction between the tested aldehydes and nitroethane was observed in the absence of the metal complex, even in the presence of nickel(II) nitrate (Table S3†).

The nature of the aromatic aldehyde greatly influences the yields and selectivity. Thus, benzaldehydes bearing the electron-withdrawing nitro substituent (Fig. 4b, c, h, j and k; Table S3,† runs 6–8, 10 and 11), in the presence of any of the catalysts 5 and 6, exhibit considerably higher reactivities compared to those of the benzaldehydes with the electron-donor methyl group in the same position (Fig. 4d, e, l and m; Table S3,† runs 13, 14 and 16, 17). This may be related with the increased electrophilicity of the aldehyde with the former substituents, which favors the nucleophilic attack of the nitronate MeCH(NO₂)⁻ to the carbonyl carbon of the aldehyde (C–C coupling step).³² The slight decrease on the yields for the ortho-nitro or -methyl benzaldehyde relative to those for the para-substituted ones can be due to the steric hindrance of the former.

The activities of the studied nickel(II)-tap complexes are much higher than those reported for other nickel(II) catalysts under similar reaction conditions, e.g., the scorpionate complex [NiCl{SO₃C(pz^Ph)₃}] (pz = pyrazolyl; 31.5% yield for benzaldehyde)²⁸ that also favors the anti isomer. A zinc(II)-tap catalyst (90% yield for benzaldehyde)⁵ is also less effective than our nickel(II)-tap complexes.

Conclusions

The system based on nickel(II)-2-amino-4-alkoxy-1,3,5-triazapentadienates catalyzes the Heck transformation of deactivated aryl halides, its efficiency strongly depending on the nature of the used room-temperature ionic liquid and the base. Moreover, the ionic liquid allows an easy separation of the product from the catalyst.

The Ni(II)-triazapentadienate centre also exhibits a good Lewis acid character which promotes the nitroethane deprotonation and the electrophilicity of benzaldehyde, thus favoring the Henry reaction.

Acknowledgements

This work has been partially supported by the Fundação para a Ciência e a Tecnologia (FCT), Portugal, through the research projects PTDC/QUI-QUI/109846/2009, PTDC/QEQ/ERQ-1648-2014 and UID/QUI/0100/2013. Y. Y. K. express gratitude to FCT for the fellowship (grant SFRH/BD/74324/2010). Authors thank the Portuguese NMR Network (IST-UTL Center) for providing access to the NMR facilities and the Portuguese MS Network (IST Node) for the ESI measurements. They also thank Susanna Sampaolesi and Massimiliano Lupacchini for their experimental assistance, in part.

Notes and references

1. M. N. Kopylovich and A. J. L. Pombeiro, Coord. Chem. Rev., 2011, 255, 339–355 , and references therein.
2. I. Haeger, R. Froehlich and E.-U. Wuerthwein, Eur. J. Inorg. Chem., 2009, 2415–2428.
3. M. Zhou, Y. Song, T. Gong, H. Tong, J. Guo, L. Weng and D. Liu, Inorg. Chem., 2008, 47, 6692–6700.
4. M. N. Kopylovich, Y. Y. Karabach, M. F. C. Guedes da Silva, P. J. Figiel, J. Lasri and A. J. L. Pombeiro, Chem.–Eur. J., 2012, 18, 899–914.
5. N. Q. Shixaliyev, A. M. Maharramov, A. V. Gurbanov, V. G. Nenajdenko, V. M. Muzalevskiy, K. T. Mahmudov and M. N. Kopylovich, Catal. Today, 2013, 217, 76–79.
6. (a) I. P. Beletskaya and A. V. Cheprakov, Chem. Rev., 2000, 100, 3009–3066; (b) N. J. Whitcombe, K. K. Hii and S. E. Gibson, Tetrahedron, 2001, 57, 7449–7476.
7. (a) B.-L. Lin, L. Liu, Y. Fu, S.-W. Luo, Q. Chen and Q.-X. Guo, Organometallics, 2004, 23, 2114–2123; (b) T. M. Gøgsig, in New Discoveries on the β-Hydride Elimination, Springer Berlin Heidelberg, Berlin, Heidelberg, 2012, pp. 81–95.
8. C. Amatore and A. Jutand, J. Organomet. Chem., 1999, 576, 254–278.
9. V. Yempally, S. Moncho, S. Muhammad, E. N. Brothers, B. A. Arndtsen and A. A. Bengali, Organometallics, 2014, 33, 3591–3595.
10. S. Z. Tasker, E. A. Standley and T. F. Jamison, Nature, 2014, 509, 299–309.
11. T. M. Gøgsig, J. Kleimark, S. O. Nilsson Lill, S. Korsager, A. T. Lindhardt, P.-O. Norrby and T. Skrydstrup, J. Am. Chem. Soc., 2012, 134, 443–452.
12. R. K. Arvela, S. Pasquini and M. Larhed, J. Org. Chem., 2007, 72, 6390–6396.
13. R. Matsubara, A. C. Gutierrez and T. F. Jamison, J. Am. Chem. Soc., 2011, 133, 19020–19023.
14. (a) T. A. P. Paulose, S.-C. Wu, J. A. Olson, T. Chau, N. Theaker, M. Hassler, J. W. Quail and S. R. Foley, Dalton Trans., 2012, 41, 251–260; (b) K. Inamoto, J.-I. Kuroda, K. Hiroya, Y. Noda, M. Watanabe and T. Sakamoto, Organometallics, 2006, 25, 3095–3098; (c) S. Ma, H. Wang, K. Gao and F. Zhao, J. Mol. Catal. A: Chem., 2006, 248, 17–20.
15. W. Zhang, H. Qi, L. Li, X. Wang, J. Chen, K. Peng and Z. Wang, Green Chem., 2009, 11, 1194–1200.
16. J. G. Huddleston and R. D. Rogers, Chem. Commun., 1998, 1765–1766.
17. J. E. L. Dullius, P. A. Z. Suarez, S. Einloft, R. F. de Souza, J. Dupont, J. Fischer and A. De Cian, Organometallics, 1998, 17, 815–819.
18. T. Suami, K. Tadano, A. Suga and Y. Ueno, J. Carbohydr. Chem., 1984, 3, 429–441.
19. T. M. Williams and H. S. Mosher, Tetrahedron Lett., 1985, 26, 6269–6272.
20. M. Shibasaki, M. Kanai, S. Matsunaga and N. Kumagai, in Bifunctional Molecular Catalysis, ed. T. Ikariya and M. Shibasaki, 2011, vol. 37, pp. 1–30.
21. W. Jin, X. Li and B. Wan, J. Org. Chem., 2010, 76, 484–491.
22. X-ray structure analysis: 5: C₆H₁₄N₈NiO₂, M_r = 288.96, monoclinic, P2₁/c, a = 7.8530(12), b = 8.1074(13), c = 9.7290(15) Å, β = 105.589(6)°, V = 596.63(16) ų, T = 296(2) K, Z = 2, ρ_calcd = 1.608 Mg m⁻³, μ = 1.632 mm⁻¹, F(000) = 300, max/min transm. = 0.829/0.731; 5824 reflections collected, 1282 unique (R_int = 0.0374); R₁ = 0.0251, wR₂ = 0.0593 (I > 2σ(I)), R₁ = 0.0372, wR₂ = 0.0632 (all data). 6: C₈H₁₈N₈NiO₂, M_r = 317.01, monoclinic, C2/c, a = 17.4047(10), b = 8.4499(5), c = 9.8847(5) Å, β = 108.668(2)°, V = 1377.24(13) ų, T = 296(2) K, Z = 4, ρ_calcd = 1.529 Mg m⁻³, μ = 1.422 mm⁻¹, F(000) = 664, max/min transm. = 0.849/0.650; 5824 reflections collected, 1260 unique (R_int = 0.0458); R₁ = 0.0358, wR₂ = 0.0859 (I > 2σ(I)), R₁ = 0.0522, wR₂ = 0.0917 (all data) CCDC 1444033 (5), 1444034 (6).
23. Typical Heck reaction conditions: [bmim][PF₆] (1.75 mmol), catalyst (0.02 mmol), and triphenylphosphine (24 mg, 0.08 mmol) were mixed in a vial (10 mL) and heated to 80 °C for 5 min in a heating block. Butyl acrylate (0.256 g, 2.0 mmol), triethylamine (0.152 g, 1.5 mmol) and the corresponding aryl halide (1.0 mmol) were then added. The mixture was then placed in the MW reactor heated to the desired temperature using up to 100 W of power.
24. N. J. Whitcombe, K. K. Hii and S. E. Gibson, Tetrahedron, 2001, 57, 7449–7476.
25. A. M. O'Mahony, D. S. Silvester, L. Aldous, C. Hardacre and R. G. Compton, J. Chem. Eng. Data, 2008, 53, 2884–2891.
26. C. Pettinari, F. Marchetti, A. Cerquetella, R. Pettinari, M. Monari, T. C. O. Mac Leod, L. M. D. R. S. Martins and A. J. L. Pombeiro, Organometallics, 2011, 30, 1616–1626.
27. M. N. Kopylovich, T. C. O. Mac Leod, K. T. Mahmudov, M. F. C. Guedes da Silva and A. J. L. Pombeiro, Dalton Trans., 2011, 40, 5352–5361.
28. B. G. M. Rocha, T. C. O. Mac Leod, M. F. C. Guedes da Silva, K. V. Luzyanin, L. M. D. R. S. Martins and A. J. L. Pombeiro, Dalton Trans., 2014, 43, 15192–15200.
29. A. Paul, A. Karmakar, M. F. C. Guedes da Silva and A. J. L. Pombeiro, RSC Adv., 2015, 5, 87400–87410.
30. M. Sutradhar, M. da Silva and A. J. L. Pombeiro, Catal. Commun., 2014, 57, 103–106.
31. Typical Henry reaction conditions: 5 μmol of catalyst, methanol (2 mL), nitroethane (4 mmol) and aldehyde (1 mmol), under air, at 25 °C, 24 h.
32. J. Boruwa, N. Gogoi, P. P. Saikia and N. C. Barua, Tetrahedron: Asymmetry, 2006, 17, 3315–3326.

---

Footnote

† Electronic supplementary information (ESI) available. CCDC 1444033 and 1444034. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra02989b

---