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J. Phys. Chem. C 2008, 112, 13524–13527
Nature of Asynchronous Hydrogen Transfer in Ketone Hydrogenation Catalyzed by Ru Complex Yue Chen,† Shubin Liu,*,‡ and Ming Lei*,† Institute of Materia Medica and Department of Chemistry, School of Science, Beijing UniVersity of Chemical Technology, Beijing 100029 P.R. China, and Renaissance Computing Institute, UniVersity of North Carolina, Chapel Hill, North Carolina 27599-3455 ReceiVed: January 15, 2008; ReVised Manuscript ReceiVed: May 11, 2008
Three different reaction pathwayssconcerted hydride transfer, concerted proton transfer, and stepwise hydrogen transfersin the carbonyl hydrogenation step of the catalytic cycle for ketone hydrogenation catalyzed by Ru complexes are investigated in this work. Our results from this study suggest that hydride and proton asynchronous transfers in the ketone hydrogenation process are stepwise in general. It is the nature of the substrate, electron withdrawing effect, and characteristics of catalytic ligands that make one of two transition states disappear in the concerted mechanism. 1. Introduction Asymmetric hydrogenation of ketones or imines is an important process in fine chemical industry and pharmaceutical synthesis.1 Bifunctional catalysts, such as Ru-diamine complexes, were first introduced and developed by Noyori et al. with high reactivity and enantioselectivity for the asymmetric hydrogenation of aromatic ketones.2-5 The homogeneous enantioselective H2-hydrogenation and transfer hydrogenation of ketones have been reported in the literature.6-10 Mechanisms of these hydrogenation reactions have extensively been examined by both experiments and theoretical calculations.6-11 For aromatic keones, great progresses have been made over asymmetric hydrogenations catalyzed by Ru complexes, but for simple dialkyl ketones the hydrogenation is still difficult.1 The overall catalytic cycle consists of carbonyl hydrogenation and catalyst regeneration (Scheme 1). In carbonyl hydrogenation, hydride on Ru and proton on amine of the catalyst are transferred to the carbon and oxygen atoms of ketone’s carbonyl group to generate alcohol and Ru-amido complex (RudN).12 Then, in the catalyst regeneration step, dihydrogen sources provide hydrogen to the Ru-amido complex.8,13,14 Aliphatic alcohols like propanol, ethanol, and methanol are usually employed as the dihydrogen source for transfer hydrogenation, whereas aromatic alcohols are rarely used for the purpose. Theoretical studies using acetone or formaldehyde as the substrate model have found that the transfer of hydride and proton was concerted but asynchronous (path A in Scheme 1), 2,12,15-18 whose midpoint is hydride transfer prior to proton with a six-memberring transition state. The mechanism was found to be different in the condensed phase.19 In this work, using the trans-dihydrido (diamine) ruthenium(II) (RuHNH) system, we propose a stepwise mechanism (path B in Scheme 1), where hydride and proton are transferred in two steps, and then we reconcile the new mechanism with the two asynchronous concerted mechanisms from the literature.2,12,15-18 * Corresponding authors. E-mail:
[email protected] (M.L.);
[email protected] (S.L.). † Beijing University of Chemical Technology. ‡ University of North Carolina.
SCHEME 1: (A) Generalized Catalytic Cycle for Ketone Hydrogenation Catalyzed by Ru Bifunctional Complex and (B) Structures of 8 Substates
2. Computational Details All optimized geometries, analytical frequencies, and other properties were calculated at the DFT B3LYP level with the LANL2DZ basis set (BS) for Ru and 6-31++G** for other atoms with the Gaussian 03 package.20 The transition states were
10.1021/jp8003807 CCC: $40.75 2008 American Chemical Society Published on Web 08/12/2008
Hydrogen Transfer in Ketone Hydrogenation
J. Phys. Chem. C, Vol. 112, No. 35, 2008 13525
Figure 1. Potential energy profiles of ketone hydrogenation for the eight substrates. a: TS1 and TS2 denote transition states of hydride and proton transfer for B1-B3, respectively.
further confirmed by the vibrational analysis and characterized by only one imaginary vibrational mode. Intrinsic reaction coordinate (IRC) calculations for A1, A4, and B1 models were performed in order to obtain the reaction paths and identify intermediates. As shown in Scheme 1, the PPh3 ligands of Ru catalyst were replaced by PH3 in the model system. Two kinds of ketones including acetone and acetophenone as substrates were used to investigate the intrinsic feature along the reaction pathway. To consider the impact of the solvent effect on the reaction, the isodensity polarized continuum model (IPCM) was applied.21 Single-point solvent energy calculations based on the optimized geometries of selected stationary points were carried out at the B3LYP/IPCM/BS level. 3. Results and Discussion Acetone (A1) and acetophenone (B1) were investigated at first. Only one transition state (TSA1) was found for A1, indicating that it takes a concerted mechanism. The structure of TSA1 is similar to the adduct (ADKA1) of A1 on RuHNH with major differences in shortened C5-H3 and H4-O6 distances and an elongated Ru1-H3 bond. Frequency analysis of TSA1 shows that the main contribution to the imaginary frequency (219.3 i) comes from the hydride between Ru and C5 of A1, and the proton (H4) has no contribution at all. Along the IRC path from TSA1 to alcohol (PA1), the C5-H3 distance is shortened rapidly from 1.80 Å to 1.24 Å with the N2-H4 bond seen little change, and then O6-H4 distance decreases from 1.45 Å to 1.0
Å with C5-H3 distance kept almost unchanged, demonstrating that it is indeed a concerted but asynchronous mechanism. Using B1 as the substrate, however, we found two transition states (TS1B1 and TS2B1) (Figure 1). TS1B1 is the transition state for hydride transfer and TS2B1 is that for proton transfer. There exists an intermediate (INTB1) between TS1B1 and TS2B1 in which C5-H3 bond (1.18 Å) is formed and N2-H4 (1.13 Å) is elongated. INTB1 can be viewed as an alkoxide ion (AI) coupled with pentacoordinated Ru complex moiety (RuNH). We noticed that TS1B1 and TSA1are similar to each other in structure. The main contribution to the imaginary frequency (165.1 i) in TS1B1 comes from the hydride (H3), and the proton (H4) has no significant contribution. For the imaginary frequencies (441.0 i) of TS2B1, the amplitude corresponds to the proton transfer process. We also noticed that, in the A1 system, even though there displays no intermediate, a terrace region has been discovered from its IRC path, whose structure looks very much like TS2B1. The structural change pattern along IRC for A1 does show a stepwise tendency, evidencing the origin of the asynchronous transfer. Aliphatic ketones and aromatic ketones exhibit different activities in asymmetric hydrogenation. Asymmetric hydrogenation for aromatic ketones often yields high enantiomeric excess (ee) percentage, but that for aliphatic ketones does not except for cyclopropyl ketones. Also, aliphatic alcohols are often used as the dihydrogen source in transfer hydrogenation but aromatic alcohols are not. Therefore, we divided the substrates into two categories (A and B) according to their aliphatic or aromatic nature (see Scheme 1B). It could reflect the influences of the electron withdrawing group (EWG) and conjugative effects of phenyl on the reaction reactivity. To further investigate the mechanism of hydride and proton transfers catalyzed by RuHNH, six other substrates were also considered (substrates A2, A3, A4, B2, B3, and B4 in Scheme 1B). We found that hydrogenation of B1, B2, and B3 belongs to the stepwise mechanism and that of B4 and category A are concerted. Table 1 shows the barrier heights and reverse barrier heights for these systems. Their potential energy profiles (Figure 1) confirm that B1, B2, and B3 each have two transition states and the energy barrier of TS1 for hydride transfer is all higher than that of TS2 for proton transfer. An electron withdrawing group on phenyl reduces the barrier height of TS1 but increases that of TS2. A1-A4 and B4 all have only one transition state, but their transition state structures are different in nature. TSA1 and TSA2 display hydride transfer like TS1, but TSA3, TSA4, and TSB4 reveal proton transfer like TS2. The impact of EWGs on energy barriers of acetone is similar since TSA1 > TSA2 and TSA3 < TSA4. Meanwhile, this work also confirms the earlier result of synchronous hydride and proton concerted transfer2,22 to the ketone catalyzed by Ru(arene) catalysts at the B3LYP level. Put together, these studies suggest that asynchronous
TABLE 1: Energy Barriers, Reverse Energy Barriers, RNH/HO, and Egap for Each System ∆ETS1a A1 A2 A3 A4 B1 B2 B3 B4
∆ETS2a
hardness of INT
∆ErTS1b
0.0820 0.0825 0.0785 0.0790 0.0795 0.0840
12.5 13.2 19.2 24.8 9.2 9.3 10.7 21.3
2.88 2.31 2.58 2.36 1.01
0.10 0.38 0.05 0.10 0.22 0.99
∆ErTS2b
2.7 2.4 3.0 2.9 2.2 0.9
RNH/HOc in INT
1.123/1.444 1.107/1.484 1.130/1.424 1.121/1.446 1.112/1.468 1.095/1.514
RNH/HOc in TS2
Egapd
1.202/1.302 1.235/1.265 1.195/1.314 1.194/1.314 1.221/1.279 1.285/1.212
0.142 0.128 0.102 0.091 0.111 0.101 0.097 0.081
a Unit kcal/mol. b Reverse energy barrier for hydride transfer (∆E rTS1) and reverse energy barrier for proton transfer (∆ErTS2), unit kcal/mol. Distances of N-H and H-O in N-H-O moiety, unit Å/Å. d Egap is the energy gap between LUMO of carbonyl and HOMO of catalyst, unit eV.
c
13526 J. Phys. Chem. C, Vol. 112, No. 35, 2008
Figure 2. Relationship between RNH/HO in INT and energy barriers from INT to ADA via TS2.
hydride and proton transfer in ketone hydrogenation processes are stepwise in general and it is the substrate or ligand of catalysts that makes one of transition states, TS1 or TS2, disappear. Also shown in Table 1 are the energy gaps (Egap) between LUMO of ketones and HOMO of catalyst, which are found to be correlated well with the energy barriers of hydride transfer of categories A and B, respectively. A smaller gap corresponds to a lower barrier or even disappearance of the transition state TS1 (like A3, A4, and B4). EWG or phenyl groups cause electrons on carbonyl to shift from oxygen to carbon and hence reduce the gap. Proton transfer is a low barrier process closely related to the stability of intermediate INT. Note that the intermediate INT is an adduct of AI on RuNH because charges and structures of AI are very similar to those of the corresponding alkoxide ion. The distance of the N2-H4-O6 hydrogen bond in INT is an indicator of the stability of INT. As the N2-H4 distance gradually decreases, O6-H4 and N2-O6 distances of INT slowly increase from A3 to A4 and from B1 to B4. The larger the ratio of N2-H4 and H4-O6 distances (RNH/HO) of INT is, the more stable the INT is (Figure 2). The RNH/HO of INT is a manifestation of the difficulty of the proton transfer (Table 1) because a larger RNH/HO signals a stronger proton affinity of AI in INT, making either the proton transfer process easier to accomplish or TS2 completely disappear (like A1 and A2). This is consistent with the stability order of these intermediates from its chemical hardness: INTA3 < INTA4, INTB1 < INTB2 < INTB3 < INTB4, and also in agreement with the barrier height order of TS2 (including TSA3 and TSA4). The good linear relationship between chemical hardness and the barrier of proton transfer for category B indicates that a stable INT makes the reaction become stepwise (see Figure 3). On the other hand, EWG and conjugation effects on phenyl can redistribute the negative change from hydride to stabilize INT and thus weaken the basicity of AI. The more negative the EWG is, the higher energy barrier of TS2 is expected. EWGs on alkyl side of aromatic ketone B4 make the energy barrier higher, as can also be witnessed by the structure of TS2 (e.g., TSA3 and TSA4). The ratio RNH/HO of TS2 reflects the proton affinity difference between Ru-amido complex (RudN) and AI in TS2, and is positively correlated to the TS2 barrier. A bigger RNH/HO ratio implies a weaker proton affinity of AI and higher energy barrier for proton transfer. We also notice that the barrier of second step (proton transfer) is low. The N2-O6 distance in INT, TS2 and ADA is around
Chen et al.
Figure 3. Relationship between chemical hardness of INT and energy barriers for B1-B4 from INT to ADA via TS2.
TABLE 2: Barrier Height of TS2 of B3 System in Six Solvents Using IPCM/B3LYP/BS benzene toluene THF isopropanol ethethanol methanol 2.25 a ∆Esolb 0.94 ∆Gsolb,c -0.35 a
2.38 7.58 0.95 1.26 -0.34 -0.03
19.92 1.41 0.12
24.55 1.44 0.15
32.63 1.46 0.17
Dielectric constant. b Unit kacl/mol. c Free energy difference.
2.58, 2.50, and 2.71 Å, respectively. The substructure N2-H4-O6 in INT forms a low barrier hydrogen bond (LBHB). In LBHB, the zero-point energy (ZPE) can play an important role in proton transfer. When ZPE is included, the barrier of proton transfer will disappear. In other words, the double-well potential energy surface changes to a single well surface and the free energy surface becomes to be single well as well. This indicates that the proton transfer is a very fast transfer process even at very low temperature. It is not the enthalpy, nor entropy, but ZPE that is responsible for the disappearance of TS2. Reduced entropy from INT to TS2 also indicates that it is an intramolecular process (see Table S4). Such an interesting phenomenon was also studied at the MP2/BS level using A1 and A4 as models (see Table S5). The structures calculated at the two levels were very close. The barriers of the two steps at MP2/BS are both higher than those at the B3LYP/BS level with the barrier of proton transfer in A4 about 2.9 kcal/mol. When ZPE is included at the MP2 level, a similar conclusion that the energy of TS2 is lower than INT can also be drawn. Again, it originates from the LBHB characteristic in proton transfer. Yet, we still can find that hydride transfer is triggered at first which in turn facilitates proton transfer as found at the B3LYP/BS level. In our model, the effect of steric hindrance has not been considered. It can be seen that the steric hindrance could lead to the increase in the N2-O6 distance and a weakening N2-H4-O6 LBHB, thus resulting in the reinstallment of the double wells and the separate step for the proton transfer process. The impact of the solvent effect on proton transfer has also been investigated, where we calculated the both energetic and free energy changes for B3 in six different solvents using the IPCM/B3LYP/BS method (see Table 2). It is observed that a polar solvent like methanol will increase the barrier height of TS2 compared with a nonpolar solvent such as benzene. With ZPE explicitly included, we find that the barrier height from INT to ADA for B3 does not completely vanish, indicating that INT is more stable in liquid phase than in gas phase. Finally, we caution that in practice no intermediate could be detected
Hydrogen Transfer in Ketone Hydrogenation in experiments for these cases described as stepwise hydrogen transfer because the hydrogenation process should be a fast process with a low barrier. 4. Conclusions In summary, asynchronous hydrogen transfer processes catalyzed by Ru complexes have been investigated in this work, such as hydride transfer (A1 and A2), proton transfer (A3, A4, and B4), and stepwise hydrogen transfer (B1, B2, and B3). We found that they are stepwise in general, and it is only the nature of the substrate that differentiates the mechanism. The barriers of reverse reactions are higher for group A than group B (except B4). The stepwise pathway of hydrogenation is benefited by the decreased barrier from the intermediate. We anticipate that the result from this study is applicable to other hydrogenation processes, providing insights in illustrating their reaction mechanisms as well as in silico catalyst design. Acknowledgment. This work was supported by Beijing Nova Fund (2005B17) and the National Natural Science Foundation of China (Grant 20703003). We also thank Chemical Grid Project at BUCT for providing part of the computational resources. S.B.L. acknowledges partial support from the Virtual Laboratory for Computational Chemistry, Computer Network Information Center, Chinese Academy of Sciences, for allowing us to access its computing facilities for the study. Supporting Information Available: Structural changes and related movies along IRC pathways of A1, A4, and B1, relationship between RNH/HO in INT/TS2 and energy barriers from INT to ADA via TS2, relative energies to corresponding R of all systems in hydrogenation. This material is available free of charge via the Internet at http://pubs.acs.org.
J. Phys. Chem. C, Vol. 112, No. 35, 2008 13527 References and Notes (1) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40. (2) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J. Org. Chem. 2001, 66, 7931. (3) Mun˜iz, K. Angew. Chem., Int. Ed. 2005, 44, 6622. (4) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am. Chem. Soc. 2003, 125, 13490. (5) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045. (6) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord. Chem. ReV. 2004, 248, 2201. (7) Cao, P.; Zhang, X. J. Org. Chem. 1999, 64, 2127. (8) Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T. Organometallics 2001, 20, 379. (9) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori, R. J. Am. Chem. Soc. 2006, 128, 8724. (10) Ma, G.; Mcdonald, R.; Ferguson, M.; Cavell, R. G.; Patrick, B. O.; James, B. R.; Hu, T. Q. Organometallics 2007, 26, 8464. (11) Di Tommaso, D.; French, S. A.; Catlow, C. R. A. Chem. Commun. 2007, 2381. (12) Samec, J. S.; Backvall, Jan-E.; Andersson, P. G.; Brandt, P. Chem. Soc. ReV. 2006, 35, 237. (13) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G. J. Am. Chem. Soc. 2005, 127, 15083. (14) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q. J. Am. Chem. Soc. 2005, 127, 3100. (15) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H J. Am. Chem. Soc. 2002, 124, 15104. (16) Handgraaf, J. W.; Reek, J. N. H.; Meijer, E. J. Organometallics 2003, 22, 3150. (17) Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Soc. 2000, 122, 1466. (18) Di Tommaso, D.; French, S. A.; Catlow, C. R. A. J. Mol. Struct. (THEOCHEM) 2007, 812, 39. (19) Handgraaf, J.; Meijer, E. J. J. Am. Chem. Soc. 2007, 129, 3099. (20) Frisch, M. J. Gaussian 03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004. (21) Foresman, J. B.; Keith, A.; Wiberg, K. B.; Snoonian, J.; Frisch, M. J. J. Phys. Chem. 1996, 100, 16098. (22) Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.; Kavana, M. J. Am. Chem. Soc. 2001, 123, 1090–1100.
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