Dinuclear salen cobalt complex incorporating Y(OTf)₃: enhanced enantioselectivity in the hydrolytic kinetic resolution of epoxides

Abstract

The activation of inactive Jacobsen’s chiral salen Co(II) (salen = N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine) compound is attained by dinuclear chiral salen Co(III)–OTf complex formation with yttrium triflate. The yttrium metal not only displays a promoting effect on electron transfer, but also assists in forming two stereocentres of a Lewis acid complex with Co(III)–OTf. We found that the binuclear Co-complex significantly enhanced reactivity and enantioselectivity in the hydrolytic kinetic resolution of terminal epoxides compared to its analogous monomer and kinetic data are also consistent with these results.

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Chiral salen metal complexes haven proven potential catalysts in various asymmetric syntheses.^1–4 Catalytic asymmetric ring opening of racemic terminal epoxides with water (hydrolytic kinetic resolution, HKR) using Jacobsen’s chiral (salen) Co^III–OAc complex as chiral catalyst has been widely applied and is highly efficient for the preparation of enantioenriched epoxides in academic and industrial sectors.^5,6

The catalytically inactive chiral salen Co^II complex is activated by aerobic oxidation via one electron transfer reaction to give a chiral salen Co^III complex; this is promoted by many Brønsted acids, which was found mechanistically to exhibit a second order dependence on the salen [Co^III] catalyst unit routed through a cooperative bimetallic mechanism.^7,8 The metal valence change from Co^III to Co^II during the HKR of racemic epoxides has been studied in detail.⁹ Further, the high reactivity, recyclability and DFT calculations of counterions/axial ligands linked to the monometallic salen Co^III unit have also been investigated, including those of the triflate ion.¹⁰

Recently, we have developed dinuclear chiral salen Co complexes bearing Lewis acids of different salts of Al, Ga, In and Tl, which proved a very good chiral catalyst in asymmetric ring opening and closing reactions.¹¹

In a continuation of our interest in activation and the development of dinuclear chiral salen complexes, herein we report the synthesis and application of a functional dinuclear salen Co^III complex (Fig. 1). Interestingly, the Y(OTf)₃ not only works as a linker, but also cooperatively activates the incoming nucleophiles and thus reduces the barrier heights in the HKR reaction of racemic terminal epoxides, which ultimately provides enhanced activity and enantioselectivity with respect to the analogous monomer. The monometallic and bimetallic chiral salen Co linked with Y(OTf)₃ were prepared by reacting the chiral salen Co^II and Y(OTf)₃ with molar ratios of 1 : 1.33 and 2 : 1.66 respectively in THF solvent at room temperature and in an open atmosphere for 40 min. After completion of reaction the solvent was removed by rotary evaporation and a crude green solid residue obtained and dried. The dried crude green solid was dissolved in CH₂Cl₂ and washed with H₂O at least three times. Concentration and evaporation of the separated CH₂Cl₂ afforded a dark green solid powder (mp > 380 °C), yield = 98–99%. The chiral salen (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino cobalt(II) (Fig. 1) and Y(OTf)₃ (purity = 98%) were procured from Aldrich and used as such.

Fig. 1 Structures of monomeric and dimeric salen Co complexes.

Continuous monitoring for the formation of oxidized salen Co dinuclear complex (Fig. 2) and quantitative estimation were performed by UV-vis spectroscopy by using the following equations.¹²

ε_Co^II_{359 nm} × [Co^II]_t + ε_Co^III_{359 nm} × [Co^III]_t = Abs_{359 nm} (1)

ε_Co^II_{419 nm} × [Co^II]_t + ε_Co^III_{419 nm} × [Co^III]_t = Abs_{419 nm} (2)

[Co^II]_t + [Co^III]_t = [Co^II]₀ (3)

Fig. 2 Continuous monitoring of UV-vis spectra for the formation of chiral [salen Co–OTf]₂Y(OTf)₃ dimer.

The values of ε for the characteristic peak of salen Co^II were calculated to be 1.168 × 10⁴ M⁻¹ cm⁻¹ at 359 nm and 1.209 × 10⁴ M⁻¹ cm⁻¹ at 419 nm by taking various concentrations of salen Co^II complex and using a linear regression method, whereas for salen Co^III we performed calculations using a numerical method based on the UV-vis spectra of salen Co^II and salen Co^III in different concentrations in these reactions with the help of the above-mentioned equations. We observed that there is complete conversion of salen Co^II to salen Co^III and the disappearance of the characteristic peak at 419 nm of salen Co^II (see kinetic profile in the ESI, Fig. S6†).

The full range general XPS survey data provide valence states of elements and very useful structural information for bimetallic salen Co bearing Y(OTf)₃ is shown in Fig. 3a. The oxidation state of cobalt(III) in bimetallic salen catalyst B was further confirmed using the Co 2p XPS spectrum where the binding energy of Co 2p_3/2 increases with the increase in the formal oxidation state of the cobalt ion.¹³ It shows Co 2p_3/2 and Co 2p_1/2 core level peaks at binding energies of 780.5 and 796.2 eV respectively (Fig. 3b) without exhibiting any complex satellite peaks always observed in the Co(II) 2p spectra. The spin–orbit splitting is found to be 15.7 eV, indicating the Co(III) oxidation state which is similar to the reported literature.¹³ The slight shifting of the binding energy peak might be possibly due to the difference in coordination environment of the salen ligand oxygen which is coordinated to Y(OTf)₃ (Fig. 1). In general, analysis of the XPS survey data of bimetallic catalyst B revealed the presence of significant peaks associated with carbon (1s = 285 eV), nitrogen (1s = 400 eV), oxygen (1s = 532 eV), fluorine (1s = 689 eV), cobalt (3s = 106 eV), yttrium (4s = 42 eV; 3d5 = 154 eV) and sulphur (2p = 169 eV; 2s = 230 eV) (Fig. 3a). ¹⁹F NMR confirms the presence of OTf, showing chemical shifts at δ = −62.70; −191.63 and −62.70; −170.93 and −191.63. The ¹H, ¹³C NMR, XRD, HRMS and FTIR data support the formation of complexes A and B (see ESI†).

Fig. 3 (a) XPS survey data of the bimetallic salen Co–Y(OTf)₃ catalyst; (b) Co 2p high resolution region.

The catalytic activities of the salen Co-complexes A and B were evaluated in the HKR of terminal epoxides and the results are summarized in Table 1. The loading values for the monomer A and binuclear B catalyst are given per [Co] salen unit. All HKR reactions were performed under solvent-free conditions except for the epoxides with aryl ethers (entries 7 and 8). Entry 2 of propylene epoxide shows the highest reactivity among the examined epoxides, affording >99% ee in a short time (1.5 h). Overall, the obtained results with the rest of the epoxides, demonstrate that the chiral salen Co dimeric complex B catalyzed the HKR of various terminal epoxides containing chloro, ether, ester and aliphatic functionalities, with good to excellent enantioselectivity (>97–99% ee) except for the compound 2-naphthyl glycidyl ether (entry 8).

Table 1 HKR of terminal epoxides catalyzed by the mono- and bimetallic catalyst A and B^a

Entry	Epoxide	Catalyst type^b	Time (h)	ee of recovered epoxide^c (%)	Yield^d (%)
a The reactions were carried out on a 10.84 mmol scale using 0.55 equiv. H2O with respect to epoxide.b Catalyst loading based on racemic epoxides and for A = 0.4 mol%; B = 0.2 mol%.c % ee was determined by chiral GC or chiral HPLC.d Isolated yield is based on racemic epoxides (theoretical maximum = 50%).e For catalyst 1 the reaction was performed at 0–4 °C with 0.5 mol% catalyst loading (ref. 8a).f Solvent THF : CH2Cl2 2 : 1 (v/v) with respect to epoxide.g THF was used as solvent.
1^e		A	12	56	20
		B	4	99.2	46
		1	16	>99	43
2		A	6	63	23
		B	1.5	99.4	42
3		A	16	74	26
		B	10	99.6	43
4		A	12	53	21
		B	2	99.7	44
5		A	12	61	23
		B	3	99.4	42
6		A	12	47	19
		B	4	99.3	44
7^f		A	12	32	12
		B	6	99.4	45
8^g		A	48	28	10
		B	24	97.1	46

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In contrast, the analogous monometallic salen Co catalyst A showed less reactivity and selectivity in comparison to its dimeric catalyst B. For all the epoxides used in the present study the k_rel were also observed to be high enough to lead to enhanced enantioselectivity for the recovered epoxides and diol products.

To elucidate the higher reactivity and enantioselectivity of the dimer catalyst B a kinetic study with epichlorohydrin (ECH) was performed and it showed a two term rate equation involving both intra- and intermolecular reaction (eqn (4)).^11b,14

Rate ∝ k_intra [catalyst] + k_inter [catalyst]² (4)

Plots of rate/[catalyst] vs. [catalyst] were linear, with slopes equal to k_inter and y-intercepts corresponding to k_intra with positive values for dimer catalyst B i.e. 36.3 M⁻¹ × min⁻¹ and 68.0 × 10⁻² min⁻¹ respectively. The monomeric catalyst A provided a y-intercept of nearly zero, revealing the absence of any first-order pathway in this HKR reaction (Fig. 4). These results are more encouraging than our previous reports.^11b,c In order to check the stability of the dimeric catalyst B during HKR reactions, a control experiment was performed and treated with an excess of water and worked up and extracted using CH₂Cl₂ solvent; the same reactivity and enantioselectivity were seen in this HKR reaction. Additionally, the catalyst B can be regenerated and re-used at least up to three cycles without any appreciable loss in activity and enantioselectivity (see ESI Fig. S35†).

Fig. 4 Kinetic study of the asymmetric HKR of epichlorohydrin catalyzed by the monomer and dimer catalysts.

These data indicate that the catalyst B exhibits better stereochemical communication, optimal transition state geometry and possibly the cooperativity of Lewis acid Y(OTf)₃ assists to activate nucleophiles which leads to enhanced enantioselectivity.

The HKR reaction catalyzed by dimeric catalyst B follows a cooperative bimetallic mechanism in a rate determining step where one salen Co unit acts as a chiral Lewis acid centre which selectively binds with matched epoxides and another serves to deliver the hydroxide nucleophile. As proposed by Jacobsen et al.,^8b these interactions are mediated by the chiral, stepped conformations of the salen ligand (Scheme 1).

Scheme 1 Proposed mechanism for the HKR of epoxides catalyzed by dimer salen Co catalyst B.

In the present HKR reaction, we propose that before forming a Co–OH or Co–OH₂ intermediate the Y(OTf)₃ support activates the water molecule in order to bring it in close proximity towards the salen Co centre and provides enhanced enantioselectivity in comparison to its monomer analogue (Scheme 2). The proposed mechanism is in complete agreement with the previously reported yttrium triflate mediated asymmetric catalysis ring opening of aziridines¹⁵ and other asymmetric reactions.¹⁶

Scheme 2 Postulated structure for the activation of nucleophiles mediated by Y(OTf)₃.

In conclusion, the dimeric salen Co catalyst bearing Y(OTf)₃ shows higher reactivity and enantioselectivity in hydrolytic kinetic resolution with various terminal epoxides than its monomer analogue. The advantage of this new catalyst is its water tolerance property due to the reasonable moisture stability of Y(OTf)₃. The roles of different rare earth metal triflates with chiral metal complexes in various asymmetric reactions are under investigation in our laboratory.

Acknowledgements

The corresponding author (S. S. Thakur) sincerely acknowledges the University Grant Commission, New Delhi for financial assistance with a UGC start-up grant [No. F.20-1/2012 (BSR)/20-1(3)-2012 (BSR)] for this work. We are thankful to Prof. Chi-How-Peng, Taiwan for helpful discussion and Dr S. P. Borikar, NCL, India for GC-analysis.

Notes and references

1. J. F. Larrow and E. N. Jacobsen, Top. Organomet. Chem., 2004, 6, 123–152.
2. S. Matsunaga and M. Shibasaki, Chem. Commun., 2014, 50, 1044–1057.
3. R. M. Clarke and T. Storr, Dalton Trans., 2014, 43, 9380–9391.
4. A. Zulauf, M. Mellah, X. Hong and E. Schulz, Dalton Trans., 2010, 39, 6911–6935.
5. (a) S. E. Schaus, B. D. Brandes, J. F. Larrow, M. Tokunaga, K. B. Hansen, A. E. Gould, M. E. Furrow and E. N. Jacobsen, J. Am. Chem. Soc., 2002, 124, 1307–1315; (b) M. Tokunaga, J. F. Larrow, F. Kakiuchi and E. N. Jacobsen, Science, 1997, 277, 936–938.
6. L. Aouni, K. E. Hemberger, S. Jasmin, H. Kabir, J. F. Larrow, I. Le Fur, P. Morel and T. Schlama, Industrialization Studies of the Jacobsen Hydrolytic Kinetic Resolution of Epichlorohydrin, in Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions, ed. H. U. Blaser and E. Schidmt, Wiley-VCH Verlag Gmbh & Co., KgaA Weinheim, Germany, 2004, pp. 165–199.
7. G.-J. Kim, H. Lee and S.-J. Kim, Tetrahedron Lett., 2003, 44, 5005–5008.
8. (a) L. P. C. Nielson, C. P. Stevenson, D. G. Blackmond and E. N. Jacobson, J. Am. Chem. Soc., 2004, 126, 1360–1362; (b) L. P. C. Nielsen, S. J. Zuend, D. D. Ford and E. N. Jacobsen, J. Org. Chem., 2012, 77, 2486–2495.
9. W. M. Ren, Y. M. Wang, R. Zhang, J. Y. Jiang and X. B. Lu, J. Org. Chem., 2013, 78, 4801–4810.
10. (a) D. D. Ford, L. P. C. Nielsen, S. J. Zuend, C. B. Musgrave and E. N. Jacobsen, J. Am. Chem. Soc., 2013, 135, 15595–15608; (b) M. R. Kennedy, L. A. Burns and C. D. Sherrill, J. Phys. Chem. A, 2015, 119, 403–409; (c) D. H. Kim, U. S. Shin and C. E. Song, J. Mol. Catal. A: Chem., 2007, 271, 70–74.
11. (a) C. K. Shin, S. J. Kim and G.-J. Kim, Tetrahedron Lett., 2004, 45, 7429–7433; (b) S. S. Thakur, W. Li, S.-J. Kim and G.-J. Kim, Tetrahedron Lett., 2004, 45, 7429–7433; (c) S. S. Thakur, S. W. Chen, W. Li, C. K. Shin, S. J. Kim, Y. M. Koo and G. J. Kim, J. Organomet. Chem., 2006, 691, 1862–1872; (d) Y. S. Kim, C. Y. Lee and G. J. Kim, Bull. Korean Chem. Soc., 2010, 31, 2973–2979; (e) P. Kumar, P. S. Chowdhury and M. Pandey, Adv. Synth. Catal., 2013, 355, 1719–1723; (f) P. Kumar and P. Gupta, Synlett, 2009, 1367–1382.
12. C. M. Liao, C. C. Hsu, F. S. Wang, B. B. Wayland and C. H. Peng, Polym. Chem., 2013, 4, 3098–3104.
13. (a) J. H. Burness, J. G. Dillard and L. T. Taylor, J. Am. Chem. Soc., 1975, 97, 6080–6088; (b) M. Volpe, H. Hartnett, J. W. Leeland, K. Wills, M. Ogunshun, B. J. Duncombe, C. Wilson, A. J. Blake, J. McMaster and J. B. Love, Inorg. Chem., 2009, 48, 5195–5207; (c) D. K. Dogutan, R. McGuire Jr and D. G. Nocera, J. Am. Chem. Soc., 2011, 133, 9178–9180; (d) D. Kochubey, V. Kaichev, A. Saraev, S. Tomyn, A. Belov and Y. Voloshin, J. Phys. Chem. C, 2013, 117, 2753–2759.
14. (a) R. G. Konsler, J. Karl and E. N. Jacobsen, J. Am. Chem. Soc., 1998, 120, 10780–10781; (b) R. Breinbauer and E. N. Jacobsen, Angew. Chem., Int. Ed., 2000, 39, 3604–3607.
15. Y. Xu, L. Lin, M. Kanai, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2011, 133, 5791–5793.
16. (a) L. Zhou, L. Lin, W. Wang, J. Ji, X. Liu and X. Feng, Chem. Commun., 2010, 46, 3601–3603; (b) W. Wang, X. Lian, D. Chen, X. Liu, L. Lin and X. Feng, Chem. Commun., 2011, 47, 7821–7823; (c) W. Li, X. Liu, F. Tan, X. Hao, J. Zheng, L. Lin and X. Feng, Angew. Chem., Int. Ed., 2013, 52, 10883–10886; (d) X. Hao, X. Liu, W. Li, F. Tan, Y. Chu, X. Zhao, L. Lin and X. Feng, Org. Lett., 2014, 16, 134–137; (e) M. Shibasaki, M. Kanai, S. Matsunaga and N. Kumagai, Top. Organomet. Chem., 2011, 37, 1–30; (f) N. Kumagai and M. Shibasaki, Angew. Chem., Int. Ed., 2013, 52, 223–234; (g) S. Matsunaga and M. Shibasaki, Synthesis, 2013, 45, 0421–0437.

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Footnote

† Electronic supplementary information (ESI) available: Catalyst preparation and characterization data. See DOI: 10.1039/c5ra12408e

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