Titanocene-Catalyzed Hydrosilylation of Imines: Experimental and

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Organometallics 2009, 28, 2546–2553

Titanocene-Catalyzed Hydrosilylation of Imines: Experimental and Computational Investigations of the Catalytically Active Species Heidrun Gruber-Woelfler and Johannes G. Khinast* Institute for Process Engineering, Graz UniVersity of Technology, 8010 Graz, Austria

Michaela Flock and Roland C. Fischer Institute of Inorganic Chemistry, Graz UniVersity of Technology, 8010 Graz, Austria

Jo¨rg Sassmannshausen Institute of Chemistry and Technology of Materials, Graz UniVersity of Technology, 8010 Graz, Austria

Tsvetanka Stanoeva and Georg Gescheidt Institute of Physical and Theoretical Chemistry, Graz UniVersity of Technology, 8010 Graz, Austria ReceiVed July 8, 2008

In this paper we communicate mechanistic investigations of the asymmetric catalytic hydrosilylation of imines using (R,R)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium (R)-1,1′-binaphth-2-olate (1) and (S,S)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium dichloride (2) as catalyst precursors. After activation with RLi (R ) alkyl, aryl) and a silane, these complexes are well-known catalysts for hydrosilylation reactions. However, the exact nature of the catalytic active species is still a subject of debate and was therefore investigated by us using experimental (IR, NMR, EPR, GC/MS) and computational methods. Our results indicate an EBTHITiRSiH2Ph compound (EBTHI ) ethylene-1,2bis(η5-4,5,6,7-tetrahydro-1-indenyl), R ) alkyl, aryl) as the catalytically active species. This Ti(IV) species is postulated to be responsible for the lower activities of 1 and 2 in contrast to hydrosilylations with ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium difluoride (3), for which a Ti(III)-H compound was postulated to be the active species. Introduction Chiral amines are important building blocks for the synthesis of a wide variety of pharmaceuticals, such as antidepressants, amphetamines, or calcimimetic drugs.1-3 Thus, considerable efforts have been devoted to the development of efficient and selective methods for the catalytic asymmetric reduction of imines to replace stoichiometric routes. In addition to catalysts based on late-transition metals,4,5 many titanocenes for enantioselective hydrogenations2,6-8 and hydrosilylations3,9-11 of imines have been developed, such as ethylene-1,2-bis(η5-4,5,6,7* Corresponding author. E-mail: [email protected]. (1) Hansen, M. C.; Buchwald, S. L. Tetrahedron Lett. 1999, 40, 2033– 2034. (2) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 8952–8965. (3) Yun, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 767–774. (4) Riant, O.; Mostefaı¨, N.; Courmarcel, J. Synthesis 2004, 2943–2958. (5) Takei, I.; Nishibayashi, Y.; Arikawa, Y.; Uemura, S.; Hidai, M. Organometallics 1999, 18, 2271–2274. (6) Vassylyev, O.; Panarello, A.; Khinast, J. G. Molecules 2005, 10, 587–619. (7) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1992, 114, 7562–7564. (8) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 11703–11714. (9) Verdaguer, X.; Lange, U. E. W.; Reding, M. T.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 6784–6785. (10) Verdaguer, X.; Lange, U. E. W.; Buchwald, S. L. Angew. Chem., Int. Ed. 1998, 37, 1103–1107. (11) Yun, J.; Buchwald, S. L. Chirality 2000, 12, 476–478.

tetrahydro-1-indenyl)titanium difluoride and other complexes. However, these catalysts are expensive and they are usually prepared under aggressive conditions (e.g., hydrofluoric acid complexes to prepare the difluoride compound12). In this paper, we communicate the asymmetric hydrosilylation of imines using two group 4 metallocenes, i.e., (R,R)-ethylene1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium (R)-1,1′-binaphth2-olate (1) and (S,S)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1indenyl)titanium dichloride (2). These complexes can be prepared easily under mild conditions and are inexpensive by comparison. The initial step of the hydrosilylation reaction involves the activation of the titanocenes with an organolithium reagent (RLi) and a silane (Scheme 1) to give an active species that catalyzes the hydrosilylation reaction. This intermediate has been studied by many research groups.2,8,10,13-16 However, the exact nature of the catalytically active species is still a subject of debate. Nevertheless, this species determines the selectivity and the (12) Reding, M. T.; Buchwald, S. L. J. Org. Chem. 1998, 63, 6344– 6347. (13) Yun, J.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 5640– 5644. (14) Woo, H. G.; Tilley, T. D. J. Am. Chem. Soc. 1989, 111, 8043– 8044. (15) Rahimian, K.; Harrod, J. F. Inorg. Chim. Acta 1998, 270, 330– 336. (16) Bareille, L.; Becht, S.; Cui, J. L.; LeGendre, P.; Moise, C. Organometallics 2005, 24, 5802–5806.

10.1021/om800643q CCC: $40.75  2009 American Chemical Society Publication on Web 03/25/2009

Titanocene-Catalyzed Hydrosilylation of Imines

Organometallics, Vol. 28, No. 8, 2009 2547

Scheme 1. Hydrosilylation of Imines with (R,R)-Ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium (R)-1,1′-Binaphth-2olate (1) and (S,S)-Ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium Dichloride (2)

Scheme 2. Activation of (S,S)-Ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyltitanium Difluoride, (S,S)-3, with PhSiH3, Pyrrolidine, and MeOH to Give a Ti(III)-H Species9

Scheme 3. Proposed Activation Mechanism of 1 and 2a

a

efficiency of the process. Thus, the involved intermediates have to be studied and, possibly, tailored to provide optimal activity and selectivity in industrial implementations. In our experimental work, reductions of N-propyl imines and cyclic imines were carried out with high yields of the corresponding amines, reaching up to 96%. However, the activity and enantioselectivity using 1 and 2 as catalytic precursors were much lower than the activity and selectivity published by Verdaguer et al.9 for the hydrosilylation of imines using the corresponding difluoride, i.e., (S,S)-ethylene-1,2-bis(η5-4,5,6,7tetrahydro-1-indenyl)titanium difluoride (3). For example, the hydrosilylation of 2-phenylpyrroline (4) at room temperature with 1 mol % of 3 afforded the corresponding amine in 97% yield and 99% ee. At least 5 mol % of the precatalyst and a reaction temperature of 63 °C are necessary to obtain similar conversions with 1. Moreover, the enantioselectivity is still lower (a maximum ee of 78% was obtained). Verdaguer et al.9 postulated that the excellent results of the hydrosilylations based on 3 can be attributed to a highly active Ti(III)-H species, which is obtained after reaction of 3 with PhSiH3, pyrrolidine, and MeOH (Scheme 2). Clearly, the differences between the results of Verdaguer et al.9 and our experiments suggest that a different active species is present, which is also supported by the fact that a different activation procedure of the precatalysts is required: While 1 and 2 need a lithium compound to be activated, 3 needs only small amounts of methanol and a base, such as pyrrolidine, for the formation of the active species (Scheme 2). The unusually high Si-F (150-166 kcal/mol) bond energy is expected to be the driving force responsible for the Ti-F (140 kcal/mol) bond cleavage.9 We believe that the reaction of 1 and 2 with an organolithium compound RLi and silane leads to a less active Ti(IV) species. A feasible mechanism for the proposed activation reaction is shown in Scheme 3. In this mechanism, the reaction of the precatalysts with 2 equiv of RLi yields a dialkyl titanium species (I in Scheme 3). While it is well known that the reaction with MeLi leads to the dimethyl compound,17-21 the exact nature of the product of the reaction with n-BuLi is not that clear. For example, Dioumaev and Harrod showed that the thermal

L2 ) EBTHI, X2 ) Cl2, binol; R ) alkyl, aryl.

decomposition of Cp2ZrBu2 at room temperature yields paramagnetic butylzirconocene(III), zirconocene(III) hydride, the diamagnetic butenylzirconocene(IV) hydride dimer, and the 1,1bis(cyclopentadienyl)-2-methyl-3-(zirconocenyl hydride)-1-zirconacyclobutane(IV) dimer.22 Independently of the structure of the dialkyl-titanocene, we expect that the addition of phenylsilane, i.e., the second activation step, replaces one alkyl group, forming a (phenylsilyl)alkyl titanium(IV) complex (II in Scheme 3). A similar (phenylsilyl)alkyl titanium(IV) complex was proposed by Harrod and Yun to be the key species in catalytic reactions using Cp2TiMe2 and PhSiH3.23 Titanocene-silyl compounds have been investigated by several research groups.20,24-28 Extended reviews on silane/transition metal interactions have been published by Corey,29 Harrod,30 Eisen,31 and Tilley.32 In order to obtain evidence for our activation theory, and furthermore, to optimize the catalyst, detailed mechanistic studies were carried out. First, the activated titanocenes were analyzed with spectroscopic methods. The experimental findings were then compared to the results obtained by density functional (17) Chien, J. C. W.; Tsai, W. M.; Rausch, M. D. J. Am. Chem. Soc. 1991, 113, 8570–8571. (18) Grossman, R. B.; Doyle, R. A.; Buchwald, S. L. Organometallics 1991, 10, 1501–1505. (19) Melillo, G.; Izzo, L.; Zinna, M.; Tedesco, C.; Oliva, L. Macromolecules 2002, 35, 9256–9261. (20) Xin, S.; Harrod, J. F. J. Organomet. Chem. 1995, 499, 181–191. (21) Grossman, R. B.; Davis, W. M.; Buchwald, S. L. J. Am. Chem. Soc. 1991, 113, 2321–2322. (22) Dioumaev, V. K.; Harrod, J. F. Organometallics 1997, 16, 1452– 1464. (23) Harrod, J. F.; Yun, S. S. Organometallics 1987, 6, 1381–1387. (24) Aitken, C. T.; Harrod, J. F.; Samuel, E. J. Am. Chem. Soc. 1986, 108, 4059–4066. (25) Chang, L. S.; Corey, J. Y. Organometallics 1989, 8, 1885–1893. (26) Hao, L.; Lebuis, A. M.; Harrod, J. F.; Samuel, E. Chem. Commun. 1997, 2193–2194. (27) Hao, L.; Lebuis, A. M.; Harrod, J. F. Chem. Commun. 1998, 1089– 1090. (28) Spaltenstein, E.; Palma, P.; Kreutzer, K. A.; Willoughby, C. A.; Davis, W. M.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 10308–10309. (29) Corey, J. Y.; Braddock-Wilking, J. Chem. ReV. 1999, 99, 175– 292. (30) Harrod, J. F. Coord. Chem. ReV. 2000, 206-207, 531. (31) Eisen, M. S. Transition-metal silyl complexes. In The Chemistry of Organic Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; John Wiley & Sons: New York, 1998; pp 2037-2128. (32) Tilley, T. D. Transition-metal silyl derivatives. In The Chemistry of Organic Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; John Wiley & Sons: New York, 2001; pp 1415-1478.

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Gruber-Woelfler et al.

Figure 1. IR spectrum of (R,R)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium-(R)-1,1′-binaphth-2-olate reacted with n-BuLi and PhSiH3 in THF.

theory (DFT) calculations using Gaussian 03.33 Lastly, the influence of (i) the catalyst, (ii) the activation base, (iii) the silane, (iv) the imine, and (v) the reaction temperature on the reaction performance (yield and selectivity) was studied.

Results and Discussion A. Experimental and Computational Investigation of the Active Species. As mentioned above, the activated titanocenes were studied by IR and NMR spectroscopy. The IR spectrum (Figure 1) of 1 treated with n-BuLi (2.5 molar equiv) and PhSiH3 (2 molar equiv) showed a peak at 2084 cm-1, characteristic for a terminal Si-H stretch mode,34,35 thus excluding a H-bridged titanocene-dimer L2-Ti-H-Ti-L2 (L2 ) EBTHI). The 29Si NMR spectrum of 1 treated with n-BuLi (2.5 molar equiv) and PhSiH3 (2 molar equiv) exhibited a signal at δ -30.62 ppm (Figure 2a) and a signal indicating excessive PhSiH3 (δ -60.13 ppm). The spectrum of 2 treated with n-BuLi (2.5 molar equiv) and PhSiH3 (2 molar equiv) showed exactly (33) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al.Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT, 2004. (34) Aitken, C.; Barry, J. P.; Gauvin, F.; Harrod, J. F.; Malek, A.; Rousseau, D. Organometallics. 1989, 8, 1732–1736. (35) Higashi, G. S.; Chabal, Y. J.; Trucks, G. W. Appl. Phys. Lett. 1990, 56, 656–658.

Figure 2. 29Si NMR of (a) 1 + n-BuLi + PhSiH3, (b) 2 + MeLi + PhSiH3, and (c) 2 + MeLi + PhSiH3+ Ph2SiH2. All spectra were collected in THF with a D2O capillary.

the same signals, indicating that in both cases the same active compound is formed. The spectrum of 1 and 2 treated with MeLi (2.5 molar equiv) plus PhSiH3 (2 molar equiv) shows signals at δ -16.6 and -35.6 ppm (Figure 2b). A comparison of these results with 29Si NMR data from the literature indicates that in this region several silanes, e.g., Ph3SiH,36 Ph2SiH2,37 or PhSiHMe2,38 can be found. Therefore, we added authentic samples of different silanes to the activated titanocenes in order to see if these compounds are generated during the activation procedure. The addition of Ph2SiH2 to activated 2 led to a new signal in the 29Si NMR spectrum at δ -33.3 ppm (see Figure 2c). Thus, we could exclude that the peak at δ -35.6 ppm results from Ph2SiH2. After adding Ph3SiH to activated 2, the spectrum also showed an additional signal, thus excluding this silane from being formed. Analysis of activated 2 by GC/MS (see Supporting (36) Rot, N.; Nijbacker, T.; Kroon, R.; de Kanter, F. J. J.; Bickelhaupt, F.; Lutz, M.; Spek, A. L. Organometallics 2000, 19, 1319–1324. (37) Beckman, J.; Dakternieks, D.; Duthie, A.; Tiekink, E. R. Z. Anorg. Allg. Chem. 2002, 628, 2948–2952. (38) Olah, G. A.; Hunadi, R. J. J. Am. Chem. Soc. 1980, 102, 6989– 6992.



Table 1. Overview of the Considered EBTHI-Based Titanocenes and the Computed IR (B3LYP/LanL2DZ), 29Si NMR, and 13C NMR Data (B3LYP/6-311+G(2d,p) GIAO and referred to TMS B3LYP/6-311+G(2d,p) GIAO, σ Si ) 327.38, σ C ) 182.46)a

a

*Carbon adjacent to the titanium. **Geometry optimization with UB3LYP/LanL2DZ.

Information) revealed a peak with an m/z signal of 136, which is consistent with the mass of PhSiHMe2. The generation of methylsilanes by reaction of dimethyl metallocenes with phenylsilane was also reported by other research groups (titanocenes,24,39 hafnocenes40). Therefore, we propose that the signal at δ -16.6 ppm results from PhSiHMe2 (literature: δ -17.6 ppm38). Interestingly, when the titanocenes were activated with n-BuLi, the formation of PhSiH2Bu or PhSiHBu2 could not be detected, either by 29Si NMR or by GC/MS analysis. In summary, the 29Si NMR and the GC/MS results yield the following conclusions: (i) the formation of the active species is independent of the starting titanocene, but depends on the activation base. (ii) The active species generated from the reaction of 1 or 2 with n-BuLi and PhSiH3 exhibits a signal at δ -30.62 ppm. (iii) The active species generated with the reaction of 1 or 2 with MeLi and PhSiH3 exhibits a signal at δ -35.62 ppm. A comparison of the experimental results of the activation of 1 and 2 with computed spectra of various potential intermediates was performed using DFT methods implemented in Gaussian03.33 We also compared our computed spectral data with experimental data of Ti-Si and Zr-Si compounds and of different silanes. A comparison of this data is given in the Supporting Information and verifies that the chosen computational methods are appropriate for the considered molecules. The computed results for different EBTHI-titanocenes are presented in Table 1. It can be seen that EBTHITibinSiH2Ph (entry 4 in Table 1) can be excluded a priori, because of the large difference between the computed and experimental 29Si (39) Samuel, E.; Harrod, J. F. J. Am. Chem. Soc. 1984, 106, 1859– 1860. (40) Sadow, A. D.; Tilley, T. D. Organometallics 2003, 22, 3577–3585.

NMR shift assigned to the active titanocenes (δ -30 ppm for the butyl compound and -35 ppm for the methyl compound). In our analysis, we also considered the existence of a dimeric structure. As a model case we computed [Cp2TiSiH2Ph]2, since the differences of the 29Si NMR shifts of the cyclopentadienyl (Cp) and the EBTHI compounds were very small (Supporting Information). As can be seen in Table 1, the difference between the signal of the active species (δ -30 and -35 ppm) and the computational value of [Cp2TiSiH2Ph]2 (δ 183.9 ppm) is large, thus excluding a dimeric structure. Since all other compounds of our considerations can be excluded, only EBTHITiSiH2Ph, EBTHITiRSiH2Ph (R ) Me, Bu), and EBTHITiHSiH2Ph remain. If an alkyl group is attached to the titanium, the carbon adjacent to the metal should show a characteristic resonance in the 13C NMR data. For EBTHITiBuSiH2Ph (entry 1 in Table 1) a chemical shift of δ 86.8 ppm (see Table 1) was calculated for this carbon. The 13C NMR spectrum of a sample that includes 1 + n-BuLi + PhSiH3 indeed exhibits a chemical shift at δ 79.3 ppm, thus excluding entry 3 (EBTHITiHSiH2Ph) and entry 5 (EBTHITiSiH2Ph) in Table 1. For EBTHITiMeSiH2Ph (entry 2 in Table 1) the chemical shift for the methyl group was computed to be δ 60.8 ppm. The experimental 13C NMR spectra of 1 + MeLi +PhSiH3 gave a resonance at δ 67.72 ppm. Although the NMR spectra were well resolved, indicating that no paramagnetic species, such as EBTHITiSiH2Ph, are present, the samples were analyzed with EPR (electron paramagnetic resonance) to investigate possible paramagnetic Ti(III) intermediates at low temperatures. Whereas 1 is EPR-silent, the EPR spectrum obtained after reacting 1 with 2.5 molar equiv of n-BuLi at room temperature and immediate freezing to 77 K shows a dominant signal at g ) 1.979 and a half-field transition at g ) 3.976 (Figure 3a).


Figure 3. EPR data of (a) 1 + BuLi and (b) 1 + n-BuLi + PhSiH3 (solvent, THF, T ) 77 K). All signals are shown at higher gain to clearly show the differences in the flanks of the dominating signals around g ) 2.

The detected EPR signal is compatible with those reported for Ti(III) species24,41-46 (see Supporting Information) and points to an asymmetric dimeric Ti(III) species formed during the reaction of 1 with n-BuLi. Upon addition of 2.5 equiv of BuLi and 2 equiv of PhSiH3 to 1 at room temperature, an intense EPR signal was observed at 77 K (g ) 1.992). It shows additional features in the flanks of the intense line pointing to the presence of more than one paramagnetic species. This indicates a Ti(III) complex that also may be present in dimeric form.47-49 As for 1 + BuLi a (somewhat weaker) half-field signal at g ) 3.983 was recorded. However, after leaving the activated metallocene for a few minutes at room temperature, no EPR signal could be detected, neither at rt nor at 77 K. The lifetime of this Ti(III) complex at room temperature is shorter than 30 s since only immediate freezing of the sample leads to their detection. At this short time scale (in terms of the reaction) also dimeric Ti(III) species are likely to be formed even in the presence of PhSiH3. Therefore, we conclude that the paramagnetic species only persist during the initial stages of the formation of the catalytically active complex and are then converted to diamagnetic products. This confirms that a (diamagnetic) Ti(IV) species predominates during the hydrosilylation reaction. In summary, the comparison of the computed and experimental results supports the hypothesis that an EBTHITiRSiH2Ph compound (R ) Me, Bu) is the catalytically active species in the hydrosilylation reactions catalyzed by activated 1 and 2. B. Mechanism of the Hydrosilylation Reaction. We also aimed at elucidating the reaction mechanism by performing detailed kinetic studies. The effects of different reaction (41) Vyshinskaya, L. I.; Korneva, S. P.; Kulikova, G. P. Russ. J. Gen. Chem. 2002, 72, 68–70. (42) Brintzinger, H. J. Am. Chem. Soc. 1967, 89, 6871–6877. (43) de Wolf, J. M.; Meetsma, A.; Teuben, J. H. Organomet. 1995, 14, 5466–5468. (44) Kru¨ger, T.; Wagner, C.; Lis, T.; Kluge, R.; Mo¨rke, W.; Steinborn, D. Inorg. Chim. Acta 2006, 359, 2489–2494. (45) Samuel, E.; Harrod, J. F.; Gourier, D.; Dromzee, Y.; Robert, F.; Jeannin, Y. Inorg. Chem. 1992, 31, 3252–3259. (46) Xin, S.; Harrod, J. F.; Samuel, E. J. Am. Chem. Soc. 1994, 116, 11562–11563. (47) Aikens, C. M.; Gordon, M. S. J. Phys. Chem. A 2005, 109, 11885– 11901. (48) Cookson, D. J.; Smith, T. D.; Pilbrow, J. R. J. Chem. Soc., Dalton Trans. 1974, 1396–1402. (49) Uppal, R.; Incarvito, C. D.; Lakshmi, K. V.; Valentine, A. M. Inorg. Chem. 2006, 45, 1795–1804.


conditions on the yield and selectivity are shown in Tables 2 and 3, respectively, where the enantioselectivity was investigated for the hydrosilylation of 4 with 1 as a catalyst precursor. A plot of the yield versus time for different catalyst concentrations and for different reaction temperatures is provided in the Supporting Information. From Table 2 it can be seen that the reaction yield is a function of the catalyst concentration and the types of organolithium, silane, and imine. The yield is not a function of the silane concentration (above a certain threshold). This is consistent with first-order kinetics with respect to imine and the catalyst (see Supporting Information). Furthermore, the type of the catalyst precursor does not affect the reaction yield, confirming that the active species is the same for the dichloride and binaphtholate complex, as shown by the mechanistic investigation of the activation. The kinetic investigations also confirm the dependence of the active species on the activation base: Our results show that the reaction rate depends on the lithium compound and decreases in the following order: n-BuLi > MeLi > PhLi. This can be attributed to the fact that for a stronger basicity of the organolithium a faster reaction is observed, since the bond breaking of the Ti-O or Ti-Cl bonds is enhanced. Additionally, steric effects might be the reason for the lower performance of the titanocenes activated by PhLi. Finally, the reaction rate strongly depends on the reaction temperature with an activation energy of 169.67 kJ/mol (see Supporting Information), yielding the rate equation

r ) -kcIccat k ) 7.98 × 1022e

-169.67[kJ/mol] RT

(1) l [ mol·s ]

(2)

In eq 1, cI is the concentration of the imine and ccat the concentration of the precatalyst in mol/L. Table 3 shows the dependence of the enantioselectivity on the reaction conditions. As can be seen, the selectivity correlates with the rate of the reaction; that is, a high selectivity is obtained at higher catalyst loadings and increased reaction temperature. Additionally, the activation with an organolithium compound with a high steric demand increases the stereoselectivity. Based on these results we propose a catalytic cycle (Figure 4) that follows a mechanism by Rahmian and Harrod.15 After the active species is generated, we propose that the first step of the catalytic cycle is the insertion of the imine into the Ti-Si bond. The resulting silylamido ligand is then displaced in a σ-metathesis step to generate the silylated amine and to regenerate the EBTHITialkylsilyl species II (Figure 4). The presence of silylamines in the hydrosilylation reactions was observed by NMR by Verdaguer et al., but they were never isolated due to their lability.9 The dependence of the enantioselectivity on the temperature and the catalyst loading with catalyst precursor 1 can be explained by this mechanism as well: after insertion of the imine into the Ti-Si bond of the active catalytic species II, an (R,R,R)sor an (R,R,S)sintermediate can be formed, leading either to the (R)- or to the (S)-amine. Our analysis of the hydrosilylations of 2-phenylpyrroline with 1 shows (see Table 3) that (S)-(-)-2-phenylpyrrolidine is preferentially formed, i.e., kS > kR. This is rather surprising, since the hydrosilylation of 2-phenylpyrroline with (S,S)-3 also leads to (S)-(-)-2-phenylpyrrolidine.9 The preference for the (S)-enantiomer indicates that the influence of the σ-substituents on the metal (i.e., the alkyl group) dominates the influence of the tetrahydroindenyl



Table 2. Hydrosilylation of Imines with Different Ethylenebis(tetrahydroindenyl) Titanocenesa mol % cat. 20 10 5 3 1 10

cat.

organolithium molar equiv PhSiH3 imine [mol/L]

imine

T [°C] yield [%]b

1

n-BuLi

1.5

0.2

2-phenylpyrroline

60

n-BuLi

1.5

0.2

2-phenylpyrroline

60

10

(S,S)-2 (rac)-2 1

1.5

0.2

2-phenylpyrroline

60

10

1

n-BuLi MeLi PhLi n-BuLi

0.2

2-phenylpyrroline

60

10

1

n-BuLi

0.8 3 10 1.5c 1.5

2-phenylpyrroline

60

10

1

n-BuLi

1.5

0.1 0.2 0.4 0.2

60

10

1

n-BuLi

1.5

0.2

2,3,4,5-tetrahydro-6-phenylpyridine N-(3,4-dihydronaphthalen-1(2H)-ylidene)propan-1-amine N-(1-phenylethylidene)propan-1-amine 2-phenylpyrroline

25 40 50 60

95.0 93.2 94.5 85.1 26.8 90.4 94.0 93.2 83.9 81.8 36.0 95.2 93.2 16.7 93.2 93.2 97.8 85.3 70.5 80.3 6.5 38.3 93.2

a 1 ) (R,R)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium (R)-1,1′-binaphth-2-olate; 2 ) ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium dichloride. b Determined with GC after 4 h reaction. Yields reported are the average of four experiments with a standard deviation of 2%. c Determined with (EtO)2MeSiH.

Table 3. Hydrosilylation of 2-Phenylpyrroline with 1: Influence of the Reaction Conditions on the Enantioselectivity cat. [mol %]a Imine [mol/L] reaction temp [°C]

base

ee [%] of (S)

0.2

63

n-BuLi

63

n-BuLi

10

0.10 0.20 0.30 0.2

n-BuLi

10 10

0.2 0.2

40 50 63 63 63

62 67 75 70 75 78 37

n-BuLi MeLi PhLi

75 75 33 51

3 5 10 10

a Refers to imine concentration. All reactions were carried out with 1.5 molar equiv of PhSiH3 (referring to imine). Enantiomeric excess (ee %) was determined by GC analysis of the corresponding trifluoroacetamides61 using Chiraldex G-TA. Reported results are an average of four reactions with a standard deviation of 5%.

ligand. The results of the experiments using different activation bases (n-BuLi, MeLi, and PhLi) confirm that the alkyl/aryl group of the organolithium compound is involved in the catalytic cycle: there is a clear difference in the reaction rate and in the steric outcome of the reaction with ee’s increasing in the following order: MeLi < PhLi < n-BuLi. Molecular models (calculated with B3LYP/LanL2DZ) of the intermediates after the imine insertion in the case of the (R)- and (S)-pathway are postulated in Figure 5. In model A the butyl group on the titanium and the phenyl group of the imine are on opposite sides. In model B this butyl group and the phenyl group are on the same side. The energetic difference between model A and B is very small (the difference between the ∆G values is 5.26 kJ/mol), indicating that due to their thermodynamic stability, the formation probability of the two molecules is almost identical. Similar results were found for the intermediates with a methyl group instead of the butyl group (i.e., the catalytically active species after activation with MeLi instead of n-BuLi); the difference between the ∆G values of the two intermediates with a methyl group was computed at 11.75 kJ/mol. However, in the next step of the catalytic cycle the incoming PhSiH3, which leads to the

Figure 4. Proposed catalytic cycle of the hydrosilylation reaction of imines with 1 and 2 (R ) butyl, methyl).

regeneration of the catalytically active species II, will attack from the front in the case A, i.e., from the same side as the alkyl group, leading to the (S)-amine, whereas in the case of B the PhSiH3 will attack from the back, i.e., from the opposite side of the alkyl group. Case A should be energetically preferred, since there is less steric hindrance between the alkyl group and the phenyl group of the imine. Therefore, the hydrosilylation of 4 leads preferentially to the (S)-amine. At low reaction temperatures and low catalyst loadings, however, the hydrosilylation may (a) proceed slowly enough to allow significant competition between the two intermediate isomers or (b) lead to a significant reverse reaction to the imines



Figure 5. Postulated structures of the intermediates A and B after the insertion of 2-phenylpyrroline into the Ti-Si bond of the catalytically active species II. In case A, the butyl group on the titanium and the phenyl group of the imine are on opposite sides; thus the incoming PhSiH3 attacks from the front. In case B, the butyl group on the titanium and the phenyl group of the imine are on the same side; thus the PhSiH3 attacks from the back. Hydrogens are omitted for clarity. The computations were carried out using B3LYP/LanL2DZ. Key distances are given in Å.

and the active species II. Both possibilities would lower the enantioselectivity of the reaction. In the case of the intermediates with the methyl group, the steric hindrance between the alkyl group and the phenyl group of the imine is generally lower, which means that the incoming PhSiH3 could also attack from the other side. Also this effect decreases the enantioselectivity of the reaction. The strong influence of the silane on the reaction rates (with (EtO)2MeSiH a yield of 17% was obtained after 24 h, whereas with PhSiH3 a yield of up to 96% was achieved) can be explained by the insertion of the imine into the Ti-Si bond of the EBTHITialkylsilyl intermediate. The smaller size of the phenylsilyl ligand results in higher rates than the rates obtained with the bulky silyl ligands generated with (EtO)2MeSiH.

To improve the performance of 1 and 2, we propose to use a bulky organolithium compound with high basicity and high steric demand (e.g., t-BuLi). Since our results showed that a higher basicity of the organolithium compound leads to higher activity, we expect that this base will lead to an enhanced activity. Furthermore, we suppose that the higher steric demand of the tert-butyl group on the titanium will lead to an increased stereoselectivity of the active species. Another possibility is to convert 1 and 2 into a Ti(III) species, e.g., by reaction with Na/Hg or LiN(CH3)28 and a silane. In addition to increasing the activity, also the enantioselectivity will be improved, since in the Ti(III)-H case the tetrahydroindenyl will influence the stereoselectivity of the reaction, thus leading to higher ee’s.

Computational Details Summary and Conclusions In this paper we report the asymmetric catalytic hydrosilylation of imines using (R,R)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium-1,1′-binaphth-2-olate (1) and (S,S)ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium dichloride (2) as catalyst precursors. The corresponding amines were obtained in high yields. However, the activity and enantioselectivity using 1 and 2 as catalytic precursors are lower than the activity and selectivity for the hydrosilylation of imines using ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium difluoride (3), indicating that a different active species is present. This active species was investigated by us using IR, NMR, and EPR spectroscopy as well as GC/MS analysis. The comparison of our computed and experimental results indicates that an EBTHITiRSiH2Ph compound (R ) alkyl, aryl) is the catalytically active species of the hydrosilylation reactions. The observed enantioselectivity of the reaction confirms that the alkyl/aryl group of the activation base is involved in the catalytic cycle; the ee values for the reaction with n-BuLi are much higher (77%) than for the reaction with MeLi (33%). Finally, the low reaction rates of the hydrosilylation with (EtO)2MeSiH confirm that the silane is involved in the structure of the active species. Based on EPR measurements, a paramagnetic Ti(III) species cannot be excluded at lower temperatures and short time scales. However, at temperatures >20 °C, the Ti(IV) species clearly dominates. This Ti(IV) species is postulated to be responsible for the lower activities of 1 and 2 in comparison to hydrosilylations with 3, where a Ti(III) intermediate was proposed to be the active species.

The geometry optimizations and the frequency calculations were performed using Gaussian0333 with the hybrid density functional B3LYP50,51 in combination with the basis set LanL2DZ, which consists of the Dunning/Huzinaga full double-ζ on first-row elements52 and Los Alamos ECP plus double-ζ beyond the first row.53-55 The NMR calculations were carried out at the B3LYP/ 6-311+g(2d,p) level of theory using the GIAO ansatz.56,57

Experimental Section General Procedures. All manipulations of air- and/or moisturesensitive materials were performed under argon using a dual vacuum/argon line and standard Schlenk techniques. THF was purified and degassed using the manual solvent purification system Pure Solve (Innovative Technology). All other solvents and chemicals were used without further purification. GC analysis was carried out on an Agilent Technologies 6890N using a HP5 5% phenyl methyl siloxane (Agilent 19091J-413) column (30.0 m × 320 µm × 0.25 µm nominal) with a flame ionization detector and nitrogen as carrier gas. GC/MS analysis: CI mass spectra were recorded with an Agilent 5973 N mass selective detector on an (50) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (51) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785–789. (52) Hay P. J., Jr. In Modern Theoretical Chemistry; Plenum: New York, 1976; pp 1-28. (53) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299–310. (54) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284–298. (55) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270–283. (56) London, F. J. Phys. Radium 1937, 8, 397. (57) Wolinski, K.; Hinton, J. F.; Pulay, P. J. Am. Chem. Soc. 1990, 112, 8251–8260.

Titanocene-Catalyzed Hydrosilylation of Imines Agilent Technologies 6890N gas chromatographer, column: HP5MS (Agilent 19091S-433), capillary: 30.0 m × 250 µm × 0.25 µm nominal, carrier gas: helium. Chiral GC was recorded with a Chiraldex G-TA (gamma cyclodextrin trifluoroacetyl) column, capillary: 30 m × 320 µm × 0 µm, carrier gas: hydrogen. 1H and 13 C NMR spectra were recorded on a Varian Inova 500 MHz spectrometer at 499.82 and 125.69 MHz, respectively. Chemical shifts are listed in delta (δ/ppm) employing residual, not deuterated solvent as internal standard (δ ) 7.24 ppm in 1H spectra and 77.0 ppm in 13C spectra for CHCl3). 29Si NMR spectra were recorded on a Bruker MSL 300 at 59.6 MHz directly from the reaction mixture using a D2O capillary as external lock or in C6D6. IR spectra were collected with a Perkin-Elmer Spectrum One spectrometer. The crude sample in THF was analyzed on a gold-die cell purged with argon. The IR signal is recorded through a KBr window over the range 450-4000 cm-1. For each spectrum 10 scans are collected. Specific rotations were determined with a Perkin-Elmer polarimeter 341. EPR spectra were collected with a Bruker ESP 300 spectrometer. The EPR samples were prepared applying the usual activation procedure: Under an argon atmosphere the metallocenes were dissolved in anhydrous THF at room temperature and n-BuLi and PhSiH3 were added. Then the samples were frozen to 77 K and the spectra were collected. Preparation of the Catalysts. (R,R)-Ethylene-1,2-bis(η5-4,5,6,7tetrahydro-1-indenyl)titanium-1,1′-binaphth-2-olate, (R,R,R)-1, and (S,S)-ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)titanium dichloride, (S,S)-2, were prepared from rac-ethylene-1,2-bis(η5-4,5,6,7tetrahydro-1-indenyl)titanium dichloride (purchased from m-cat GmbH) following a procedure reported by Chin and Buchwald.58 1 H NMR (R,R,R)-1 δ (CDCl3) 7.79 (d, 2H, J ) 8.3 Hz), 7.76 (d, 2H, J ) 8.3 Hz), 7.16 (t, 2H, J ) 7.3 Hz), 7.10 (d, 2H, J ) 8.3 Hz), 7.02 (t, 2H, J ) 8.3 Hz), 6.89 (d, 2H, J ) 8.9 Hz), 5.56 (m, 4H), 3.33 (m, 2H), 3.09 (m, 2H), 2.62-2.49 (m, 4H) 1.77-1.63 (m, 6H), 1.51-1.44 (m, 4H), 1.20 (m, 2H); 13C NMR (R,R,R)-1 δ (CDCl3) 165.7, 137.3, 134.8, 133.0, 128.7, 128.5, 127.7, 127.1, 125.6, 125.2, 121.9, 121.6, 117.9, 116.3, 106.5, 27.6, 24.0, 23.3, 22.2, 21.9; [R]58925 -3768 ( 11 (c 3.8 mg/10 mL CH2Cl2). 1 H NMR (S,S)-2 δ (CDCl3) 6.6 (d, 2H, J ) 3 Hz), 5.55 (d, 2H, J ) 3 Hz) (Cp-Hs), 3.3-3.0 (m, 6H), 2.63-2.59 (m, 4H), 2.39-2.34 (m, 2H), 1.96-1.84 (m, 4H), 1.56-1.52 (m, 4H); 13C NMR (S,S)-2 δ (CDCl3) 138.1, 135.0, 129.2, 126.6, 111.8, 28.1, 24.8, 24.4, 22.02, 21.99; [R]58925 +717 ( 4 (c 3.6 mg/10 mL CH2Cl2). Preparation of the Imines. 2-Phenylpyrroline (4) and 2,3,4,5tetrahydro-6-phenylpyridine (5) were prepared following a synthesis by Coindet et al.59 Yield 4: 85.5%; GC/MS tR ) 18.857; MS (m/z) 186, 174, 146 (M+), 117, 104, 91, 57; 1H NMR δ (CDCl3) 7.87 (2H, dd, J ) 1.47, 7.81 Hz), 7.44 (3H, m), 4.06 (2H, tt, J ) 1.96 Hz, 7.32 Hz), 2.98 (2H, m), 2.04 (2H, m); 13C NMR δ (CDCl3) 174.25, 134.1, 131.0, 128.7, 128.1, 61.2, 35.2, 22.7. Yield 5: 83.4%; GC/MS tR ) 20.65; MS (m/z) 200, 188, 160 (M+), 144, 132, 82, 57; 1H NMR δ (CDCl3) 7.66 (2H, m), 7.26 (3H, m), 3.72 (2H, t, J ) 5.86 Hz), 2.52 (2H, t, J ) 6.35 Hz), 1.72 (2H, m), 1.57 (2H, m); 13C NMR δ (CDCl3) 165.9, 140.5, 129.7, 128.4, 126.1 50.12, 27.2, 22.1, 20.0. (58) Chin, B.; Buchwald, S. L. J. Org. Chem. 1996, 61, 5650–5651. (59) Coindet, C.; Comel, A.; Kirsch, G. Tetrahedron Lett. 2001, 42, 6101–6104.

Organometallics, Vol. 28, No. 8, 2009 2553 N-(3,4-Dihydronaphthalen-1-(2H)-ylidene)propan-1-amine (6) and N-(1-phenylethylidene)propan-1-amine (7) were prepared according to Cobas et al.60 Yield 6: 85.96%; GC/MS tR ) 22.306; MS (m/z) 228, 216, 188 (M+), 172, 158, 146, 57; 1H NMR δ (CDCl3) 8.10 (1H, dd, J ) 1.46, 7.81), 7.21-7.06 (3H, m), 3.33 (2H, t, J ) 7.32 Hz), 2.72 (2H, t, J ) 6.35 Hz), 2.50 (2H, t, J ) 6.35 Hz), 1.85 (2H, m), 1.71 (2H, m), 0.94 (3H, t, J ) 7.32 Hz); 13C NMR δ (CDCl3) 164.5, 140.6, 135.1, 129.7, 128.5, 126.6, 125.8, 53.0, 30.1, 28.0, 24.5, 22.9, 12.5. Yield 7: 86.4%; GC/MS tR ) 18.126; MS (m/z) 202, 190, 162 (M+), 146, 132, 84, 57; 1H NMR δ (CDCl3) 7.71 (2H, m), 7.23 (3H, m), 3.32 (2H, t, J ) 6.83 Hz), 2.11 (3H, s), 1.63 (2H, m), 0.91 (3H, m); 13C NMR δ (CDCl3) 165.2, 141.8, 128.5-126.8 (5C), 54.2, 24.4, 15.8, 12.4. Hydrosilylation. For the hydrosilylation reaction the metallocene was dissolved in anhydrous THF in a dry Schlenk flask under an argon atmosphere. After the organolithium compound, the silane and the imine were added and the mixture was heated to the appropriate reaction temperature. The reaction progress was monitored via GC until no further reaction progress could be determined. Then the mixture was allowed to cool to room temperature, and the reaction was quenched with diethyl ether and HCl (1 M). This biphasic mixture was stirred in open air for 20 min, the layers were separated, and the organic layer was washed with HCl. For neutralization NaOH was added and the aqueous layer was washed with diethyl ether. The combined organic layers were dried over Na2SO4 and reduced in Vacuo to give the corresponding amines as oils. The amines were characterized via GC/MS and NMR. 2-Phenylpyrrolidine: GC/MS tR ) 19.222; MS 146 (M+), 118, 104, 91, 57; 1H NMR δ (CDCl3) 7.35-7.31 (4H, m), 7.22-7.21 (1H, m), 4.07 (1H, t, J ) 7.5 Hz), 3.13-3.09 (2H, m), 2.2-2.1 (2H,m), 1.98 (bs, 1H), 1.77-1.60 (m, 1H); 13C NMR δ (CDCl3) 143.9, 130.6. 128.7, 127.8, 127.3, 126.9, 62.9, 47.0, 34.3, 25.6. 2-Phenylpiperidine: GC/MS tR ) 19.132; MS 202, 190, 162 (M+), 145, 134, 84, 57. N-Propyl-1,2,3,4-tetrahydronaphthalen-1-amine: GC/MS tR ) 22.215; MS 218, 190 (M+), 159, 131, 57. N-(1-Phenylethyl)propan-1-amine: GC/MS tR ) 18.024; MS 192, 164 (M+), 148, 133, 105, 57.

Acknowledgment. We kindly acknowledge the financial support by the Austrian Science Fund (Project No. 19410). Supporting Information Available: Comparison of experimental and computed IR and 29Si NMR data; overview of EPR data of titanium-silyl compounds; IR spectra of 1, 1 reacted with n-BuLi, and 2 activated with n-BuLi and PhSiH3; GC/MS spectra of 1 reacted with MeLi and PhSiH3, and kinetic data as well as Cartesian coordinates of the optimized geometries. This material is available free of charge via the Internet at http://pubs.acs.org. OM800643Q (60) Cobas, A.; Guitian, E.; Castedo, L. J. Org. Chem. 1993, 58, 3113– 3117. (61) Langlois, N.; Dang, T. P.; Kagan, H. B. Tetrahedron Lett. 1973, 14, 4865.

Titanocene-Catalyzed Hydrosilylation of Imines: Experimental and

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