Carbon–carbon bond forming reactions of N-bound transition metal α-cyanocarbanions: a mechanistic probe for catalytic Michael reactions of nitriles

Abstract

N-Bound α-cyanocarbanion complexes Ru⁺Cp(NCCH⁻R¹)(PPh₃) ₂ 1 react with electron deficient olefins to afford the conjugate adduct Ru⁺Cp(NCC⁻R¹CHR²CR³ R⁴)(PPh₃)₂ 2, kinetic studies of which revealed that complex 1-catalyzed Michael reactions of nitriles proceed via transformation of 1 to 2 and subsequent ligand exchange with nitriles.

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Transition metal α-cyanocarbanions have attracted much attention as active species for stoichiometric¹ and catalytic^2,3 carbon–carbon bond formations of nitriles, and studies on their structure and reactivity^4,5 are particularly of importance to develop novel transformations of nitriles bearing high selectivities, atom efficiency and sustainability.⁶ In 1989 we presented a new methodology for catalytic carbon–carbon bond formation of nitriles initiated by α-C–H activation of nitriles with low-valent transition metal catalysts.^2a Capture of the α-cyanocarbanion intermediate with electrophiles provides a family of catalytic C–C bond formations at the α-position of nitriles under neutral conditions.²N-Bound α-cyanocarbanion complexes, mer-Ru⁺H(NCCH⁻CO₂R)(NCCH ₂CO₂R)(PPh₃)₃, derived by α-C–H activation of alkyl cyanoacetates with RuH₂(PPh₃)₄, have proven to be reactive species and active catalysts for the RuH₂(PPh₃)₄-catalyzed aldol and Michael reactions of nitriles.^2b,7 Further studies revealed that a variety of N-bound transition metal α-cyanocarbanion complexes act as efficient catalysts for the aldol and Michael reactions of nitriles.⁸

One of the most important aspects of this chemistry is to clarify and control the C–C bond forming process on the α-cyanocarbanion intermediates. Direct nucleophilic attack of zwitterionic N-bound α-cyanocarbanions to carbon electrophiles has been postulated for the crucial step in these catalytic aldol and Michael reactions.^2b,3b,7,8 Isomerization to C-bound α-cyanocarbanions⁵ and subsequent carbometallation¹ are alternative possibilities for this process; however, precise mechanistic information on this step still remains to be explored. During the course of our systematic studies on the structure and reactivity of transition metal α-cyanocarbanions⁵ we have succeeded in the isolation of intermediate for catalytic Michael reactions of nitriles. We describe here the conjugate addition of N-bound α-cyanocarbanions, Ru⁺Cp(NCCH⁻R)(PPh₃)₂ 1 to electron deficient olefins, and mechanism of the catalytic Michael reactions of nitriles.⁹

When a 25.0 mM solution of N-bound α-cyanocarbanion Ru⁺Cp(NCCH⁻SO₂Ph)(PPh₃) ₂⁵1a in benzene was allowed to react with dimethyl ethylidenemalonate (1.0 equiv.) at room temperature under argon atmosphere, conjugate addition and subsequent 1,3-hydrogen shift occurred to give the corresponding N-bound α-cyanocarbanion Ru⁺Cp[NCC⁻(SO₂Ph)CHMeCH(CO₂ Me)₂](PPh₃)₂2a in 99% isolated yield. Complex 2a was characterized by ¹H, ¹³C{¹H}, ³¹P{¹H} NMR, IR, mass spectra and elemental analysis.§ Characteristic downfield shifts of the IR absorption (2153 cm⁻¹) and ¹³C NMR signal (δ 143.7) of the cyano group indicate that the α-cyanocarbanion is N-bound,¶ and the zwitterionic structure has been unequivocally established by a ¹H–¹³C HMBC experiment.|| Similar treatment of cyanoacetate and ketonitrile analogs 1b (R¹ = CO₂Et)^8d and 1c (R¹ = COBu^t) gave the corresponding adducts 2b, c in 98 and 98% isolated yields. Various electron deficient olefins such as dimethyl benzylidenemalonate, benzylidenemalononitrile, pent-3-en-2-one, and acrylonitrile reacted smoothly with 1a at room temperature to afford 2d–g in 98, 99, 31 and 36% yields, respectively.

As well as complex 1,^8d complex 2 shows comparable catalytic activity for the Michael additions of nitriles. Typically, the reaction of (phenylsulfonyl)acetonitrile 4 (4.00 M) with dimethyl benzylidenemalonate 3 (4.40 M) in the presence of 1a or 2d catalyst (0.120 M) in THF at 25 °C for 24 h gave adduct 5 in 86 and 88% isolated yields, respectively. In order to obtain insight into the mechanism of the complex 1-catalyzed Michael addition of nitriles, kinetic studies on the reaction of 1a with an excess amount of 3 in THF-d₈ were carried out by means of ¹H NMR (500 MHz) analysis using an internal standard (bibenzyl). The consumption rate of 1a exhibited clean pseudo-first-order dependence on the concentration of 1a (k_obs = 6.61 ± 0.04 × 10⁻⁴ s⁻¹ at 25.0 °C, [1a]₀ = 2.00 × 10⁻² M, [3]₀ = 2.00 × 10⁻¹ M), and the k_obs values showed linear dependence on the initial concentration of 3 ranging from 2.00 to 4.00 × 10⁻¹ M, indicating the second-order rate constant k₁ as 2.9 ± 0.1 × 10⁻³ dm³ mol⁻¹ s⁻¹ at 25.0 °C. Dependences of k_obsvs. [3]₀ at 25.0–45.0 °C are shown in Fig. 1. The rate data correlate well (R² = 0.990) with the Arrhenius relationship of ln(k₁) vs. 1/T, where the ΔH^‡ and ΔS^‡ values were determined as 41 ± 3 kJ mol⁻¹ and −148 ± 8 J mol⁻¹ K⁻¹, respectively. The second-order kinetics and the large negative value of ΔS^‡ clearly indicate that the conjugate addition of 1a to 3 proceeds via a direct ionic pathway without any contact of olefins with the metal center. Ru⁺Cp[NCCH(SO₂Ph)CHMeC⁻(CO₂ - Me)₂](PPh₃)₂ could not be detected during ¹H NMR experiments, indicating that the process involves a fast 1,3-hydrogen shift after the conjugate addition. When complex 2d was allowed to react with nitrile 4 at room temperature in THF-d₈, dissociation of Michael adduct 5 and regeneration of complex 1a can be monitored by ¹H NMR spectroscopy. The consumption rate of 2d was first-order on the concentration of 2d ([2d]₀ = 2.00 × 10⁻² M, [4]₀ = 2.00 × 10⁻¹ M) and independent on the concentration of 4 ([4]₀ = 2.00–3.50 × 10⁻¹ M). The first-order rate constant k₂ was determined to be 7.3 ± 0.3 × 10⁻⁶ s⁻¹ at 25.0 °C. The observed first-order kinetics on the ligand exchange process is ascribed to rate-determining formation of the 16-electron complex [RuCp(PPh₃)₂]⁺ which would be followed by fast rebound process of the carbanion of 4 from outer sphere of the metal.

Fig. 1 Dependence of k_obsvs. [3]₀ for the reactions of 1a with 3 in THF-d₈ at 25.0 °C (●), 30.0 °C (○) 35.0 °C (■), 40.0 °C (□) and 45.0 °C (▲).

The complex 1a-catalyzed Michael reaction of nitrile 4 with olefin 3 can be rationalized by the mechanism shown in Scheme 1. Direct ionic addition of 1a to 3 and a subsequent 1,3-hydrogen shift affords complex 2d, which undergoes a rate determining process of ligand exchange with 4 to form adduct 5 and regenerate catalyst 1a. In order to verify this mechanism, kinetics on the overall catalytic Michael reaction of 4 with 3 were carried out at 25.0 °C in THF-d₈ using the same NMR technique. The initial rate of the formation of 5 was constant (d[5]/dt = k_obs = 1.44 ± 0.03 × 10⁻⁷ dm³ mol⁻¹ s⁻¹), when the reaction was started at an initial concentration of [1a]₀ = 2.00 × 10⁻² M, [3]₀ = 2.00 × 10⁻¹ M and [4]₀ = 2.00 × 10⁻¹ M. Almost the same k_obs value of 1.49 ± 0.03 × 10⁻⁷ dm³ mol⁻¹ s⁻¹ was obtained when complex 2d was employed as the catalyst ([2d]₀ = 2.00 × 10⁻² M). These rate constants are first-order on the concentration of catalyst 1a or 2d, and zero-order on the concentration of both nitrile 4 and olefin 3. Thus, the rate law for the catalytic reaction can be expressed as d[5]/dt = k₃[Ru] ([Ru] = [1a]₀ = [2d]₀ = [1a] + [2d]), which leads to the relation k₃ = k_obs/[Ru]. The calculated k₃ value of 7.7 ± 0.9 × 10⁻⁶ s⁻¹ (25.0 °C) is well in accord with that of k₂; the rate constant of rate-determining step of the proposed catalytic cycle.

Scheme 1

In summary, we have identified the active species of the catalytic Michael reactions of nitriles, and presented a definitive mechanism for the reactions. This is a rare case because most reported mechanistic investigations for catalytic Michael reactions of nitriles deal mainly with substrate and product analysis while speculating on the crucial step of carbon–carbon bond formation. Efforts are currently underway to investigate more fully the dynamic behavior of transition metal α-cyanocarbanion intermediates in a variety of carbon–carbon bond forming processes of nitriles.

Acknowledgements

This work was supported by Research for the Future program, the Japan Society for the Promotion of Science, and a Grant-in-Aid for Scientific Research, the Ministry of Education, Science, Sports, and Culture, Japan.

Notes and references

1. P. Knochel, N. Jeong, M. J. Rozema and M. C. P. Yeh, J. Am. Chem. Soc., 1989, 111, 6474; H.-J. Liu and N. H. Al-said, Tetrahedron Lett., 1991, 32, 5473; T. Kauffmann, H. Kieper and H. Pieper, Chem. Ber., 1992, 125, 899; M. T. Reetz, H. Haning and S. Stanchev, Tetrahedron Lett., 1992, 33, 6963.
2. (a) T. Naota, H. Taki, M. Mizuno and S.-I. Murahashi, J. Am. Chem. Soc., 1989, 111, 5954; (b) S.-I. Murahashi, T. Naota, H. Taki, M. Mizuno, H. Takaya, S. Komiya, Y. Mizuho, N. Oyasato, M. Hiraoka, M. Hirano and A. Fukuoka, J. Am. Chem. Soc., 1995, 117, 12436; (c) H. Takaya, T. Naota and S.-I. Murahashi, J. Am. Chem. Soc., 1998, 120, 4244.
3. (a) S. Paganelli, A. Schionato and C. Botteghi, Tetrahedron Lett., 1991, 32, 2807; (b) M. Sawamura, H. Hamashima and Y. Ito, J. Am. Chem. Soc., 1992, 114, 8295; (c) Y. Yamamoto, M. Al-Masum and N. Asao, J. Am. Chem. Soc., 1994, 116, 6019; (d) B. M. Trost, P.-Y. Michellys and V. J. Gerusz, Angew. Chem., Int. Ed. Engl., 1997, 36, 1750.
4. S. D. Ittel, C. A. Tolman, A. D. English and J. P. Jesson, J. Am. Chem. Soc., 1978, 100, 7577; J. G. Stack, J. J. Doney, R. G. Bergman and C. H. Heathcock, Organometallics, 1990, 9, 453; G. L. Crocco, K. E. Lee and J. A. Gladysz, Organometallics, 1990, 9, 2819; J. S. Ricci and J. A. Ibers, J. Am. Chem. Soc., 1971, 93, 2391.
5. T. Naota, A. Tannna and S.-I. Murahashi, J. Am. Chem. Soc., 2000, 122, 2960 and references therein..
6. S.-I. Murahashi and T. Naota, Bull. Chem. Soc. Jpn., 1996, 69, 1805.
7. Y. Mizuho, N. Kasuga and S. Komiya, Chem. Lett., 1991, 2127.
8. Ru⁺H(NCCH⁻CO₂R)(dppe)₂ : (a) M. Hirano, A. Takenaka, Y. Mizuho, M. Hiraoka and S. Komiya, J. Chem. Soc., Dalton Trans., 1999, 3209 Re⁺(NCCH⁻CO₂R)(NCCH₂ CO₂R)(PMe₂Ph)₄:; (b) M. Hirano, Y. Ito, M. Hirai, A. Fukuoka and S. Komiya, Chem. Lett., 1993, 2057; (c) M. Hirano, M. Hirai, Y. Ito, T. Tsurumaki, A. Baba, A. Fukuoka and S. Komiya, J. Organomet. Chem., 1998, 569, 3 RuCp⁺(NCCH⁻- CO₂R)(PPh₃)₂:; (d) S.-I. Murahashi, K. Take, T. Naota and H. Takaya, Synlett, 2000, 1016.
9. A preliminary result has been presented: 74th Annual Meeting of the Chemical Society of Japan, Kyotanabe, March 27–30, 1998, Paper 3A117..

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Footnotes

† Electronic supplementary information (ESI) available. Experimental section. See http://www.rsc.org/suppdata/cc/b0/b007517p/

‡ Dedicated to Professor J. F. Normant on the occasion of his 65th birthday.

§ Characterization data for 2a: mp 110 °C (decomp.). IR (KBr) 2153 (CN), 1732 (C[double bond, length half m-dash]O), 1480, 1433, 1281 (C–O, S[double bond, length half m-dash]O), 1134 (S[double bond, length half m-dash]O), 1090, 745, 696, 610 cm⁻¹; ¹H NMR (500 MHz, C₆D₆) δ 1.26 (d, J 7.0 Hz, 3 H, CHCH₃), 3.27 (s, 3 H, OCH₃), 3.37 (s, OCH₃), 3.63 (dq, J 9.6, 7.0 Hz, 1 H, CH³CH₃), 4.11 [d, J 9.6 Hz, 1 H, CH⁴(CO₂CH₃)₂], 4.44 (s, 5 H, C₅H₅), 6.92–7.02 (m, 21 H, ArH), 7.36–7.44 [m, 12 H, PC₆H₅ (ortho)], 8.07 [dd, J 8.0, 2.5 Hz, 2 H, SO₂C₆H₅ (ortho)]; ¹³C{¹H} NMR (126 MHz, C₆D₆) δ 169.5 (C[double bond, length half m-dash]O), 169.4 (C[double bond, length half m-dash]O), 150.9 [SO₂C₆H₅ (ipso)], 143.7 (CN), 137.9 [PC₆H₅ (ipso)], 134.0 [SO₂C₆H₅ (ortho)], 133.8 [PC₆H₅ (ortho)], 129.3 [SO₂C₆H₅ (para)], 129.2 [PC₆H₅ (para)], 128.5 [PC₆H₅ (meta)], 126.4 [SO₂C₆H₅ (meta)], 83.6 (C₅H₅), 59.9 [CH(CO₂CH₃)₂], 58.7 (CCN), 52.0 (OCH₃), 51.6 (OCH₃), 34.2 (CHCH₃), 20.4 (CH₃); ³¹P{¹H} NMR (202 MHz, C₆D₆) δ 43.2 (s); FAB-MS: m/z 1030 ([M]⁺). Anal. Calc. for C₅₆H₅₁NO₆P₂RuS: C, 65.4; H, 5.00; N, 1.36. Found: C, 65.5; H, 4.82; N, 1.36%.

¶ A variety of N-bound complexes RuCp⁺(NCCH⁻SO₂Ph)(PR₃) ₂ show IR absorption for the CN triple bond in the range ca. 2150–2170 cm⁻¹, and ¹³C chemical shift of a nitrile carbon at δ 140–155, while those of the C-bound isomers have been observed at 2190–2200 cm⁻¹ and δ 110–125, respectively.⁵

|| The ¹H NMR signal of 2a appearing at δ 4.11 strongly correlates with ¹³C signals of two carbonyl carbons (δ 169.4 and 169.5), which clearly leads to assignment of the ¹H signal as the H⁴ proton of the zwitterionic α-cyanocarbanion moiety.

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