Communication pubs.acs.org/Organometallics
Direct H/OR and OR/OR′ Metathesis Pathways in Ester Hydrogenation and Transesterification by Milstein’s Catalyst Faraj Hasanayn* and Abdulkader Baroudi Department of Chemistry, The American University of Beirut, Beirut, Lebanon S Supporting Information *
ABSTRACT: Using DFT calculations we identify a low-energy reaction path connecting methyl acetate and Milstein’s trans-[Ru(H)2(PNN)(CO)] catalyst directly with acetaldehyde and trans-[Ru(H)(OMe)(PNN)(CO)]. The transformation represents a metathesis in which a hydride and an alkoxide are swapped between a metal center and an acyl group. The reaction leads to a simple mechanism systematically applicable to the diverse hydrogenation and dehydrogenative coupling chemistry that can be achieved by the given catalyst.
T
he square-pyramidal [Ru(PNN)(CO)(H)] (1-Ru; eq 1) is a prototype of pincer-ligated complexes that add H2 reversibly via a metal−ligand cooperation mode to give octahedral trans-Ru−dihydride products (1-Ru-H).1
An elaborate DFT investigation by Wang et al. (presented in the coupling direction) predicted the more favorable route for eq 4 to follow an outer-sphere Noyori-type mode in which a hydride from the metal and a proton from the ligand are transferred, sequentially, to the carbonyl without prior coordination of the ester to the metal.27
The Milstein group discovered that 1-Ru-H catalyzes under neutral homogeneous conditions the otherwise challenging hydrogenation of esters (eq 2),2 carboxamides (eq 3),3 organic carbonates and carbamates,4 and urea.5
Remarkably, the Milstein group could adapt the reversibility of eq 1 to catalyze the reverse of eqs 2 and 3, producing esters6 and carboxamides7 cleanly from alcohols and amines with H2 as the only byproduct. There is at present great interest in utilizing such methods in green chemistry, from hydrogenation to polypeptide synthesis, and in important contemporary applications such as biomass production of H2 and CO2 fixation.1−25 1-Ru has been commercialized, and new classes of catalysts have been discovered17−24 and recently reviewed.25 The rapid advancements in the given chemistry have not been matched with a definitive mechanistic understanding. The initial report on ester hydrogenation by 1-Ru-H proposed a (bifunctional) metal−ligand cooperation mechanism producing 1-Ru and hemiacetals as intermediates (eq 4), and this remains a generally accepted mechanism.26 © XXXX American Chemical Society
Figure 1. Energies of four outer-sphere TSs for hydride transfer from 2-Ru-H to 3. Values are given in kcal/mol relative to the separated 2−Ru-H and 3. M06-PCM results were calculated at 298 K and 1 atm.
The trans-dihydride configuration in 1-Ru-H is expected to weaken the Ru−H bonds;28,29 thus, an outer-sphere hydride transfer to a carbonyl is a plausible entry step to hydrogenation in general. Herein work we report DFT results which show without ambiguity that hydride transfer from 1-Ru-H to esters can lead directly to aldehydes and Ru−alkoxides, thereby Received: February 12, 2013
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dx.doi.org/10.1021/om400122n | Organometallics XXXX, XXX, XXX−XXX
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Figure 2. Calculated Horel and Gorel values of TSs and minima on the PES in the reaction between 2-Ru-H and 3 along path a2 defined in Figure 1. M06 results are given in kcal/mol at 298 K and 1 atm using a PCM representing THF as solvent. Bond distances are given in Å.
The net transformation in Figure 2 is an unconventional organometallic metathesis in which a hydride and an alkoxide are swapped between a metal center and an acyl group. The key to the process lies in the ability of the metal to alternate the activation of the C−H and C−OR bonds of the hemiacetal oxide by respectively coordinating the H and OR groups. A third possibility here would be the coordination of the terminal oxygen of the hemiacetaloxide to yield the octahedral 2-RuHemAc shown in Figure 3, which is calculated to have a slightly
solving the challenging part of the hydrogenation problem in one step. The study has been carried out at the M06-PCM level of theory on the reaction between the dimethylamine analogue of 1-Ru-H (2-Ru-H) and methyl acetate (3). Four outer-sphere reaction pathways have been considered, as described in Figure 1. Three of the paths afford relatively low enthalpies of activation (5.8−7.5 kcal/mol) for the hydride transfer step. For our purposes it is most convenient to follow the PES past hydride transfer along path a2. The results are summarized in Figure 2. Hydride transfer from 2-Ru-H to 3 gives at first an ion-pair (IP) minimum between a square-pyramidal cation and a hemiacetaloxide anion (3-IP-H) in which the new C−H bond is pointed toward Ru at a distance (2.04 Å) close to that in the TS (1.95 Å). The new C−H bond itself is long in 3-IP-H at 1.27 Å, in comparison to 1.14 Å in the free hemiacetaloxide. 3IP-H has a similar energy as the preceding TS and hence represents an activated point on the PES that is prepared to undergo further transformation. In path a under consideration the methylene protons of the phosphine arm of the ligand are not available for immediate proton transfer to produce a hemiacetal. In the absence of a strong covalent bond between the two ions, the hemiacetal oxide should be able to reorganize with respect to the metal. Indeed, a trivial displacement of the hemiacetaloxide in the direction that brings the methoxy oxygen closer to the metal center leads to a new minimum on the PES (3-IP-OR) that is 3.0 kcal/mol below 3-IP-H. The two IP minima are connected by 3-TS-slip with Horel and Gorel values of 11.6 and 19.5 kcal/ mol, respectively, above the separated reactants, indicating that the population of 3-IP-OR is not kinetically prohibitive. 3-IP-OR is characterized by a long distance between Ru and the methoxy oxygen (2.41 Å) and an elongated C−OMe bond (1.60 Å). In the free hemiacetaloxide the C−OMe bond is 1.55 Å. Thus, slippage past hydride transfer is thermodynamically favorable and at the same time it activates the C−OMe bond. Consistently, the PES has a TS for C−OMe bond cleavage (3TS-OR) that is less than 1 kcal/mol above 3-IP-OR. C−OMe cleavage leads at first to an adduct between acetaldehyde and an octahedral Ru−alkoxide with C−OMe = 2.80 Å and Horel = 0.9 kcal/mol. The dissociated acetaldehyde and 2-Ru-OMe are 8.2 kcal/mol above the separated reactants.
Figure 3. Three reactions that can be mediated by ion-pair formation and rearrangement. Energies are given in kcal/mol.
negative Horel. In fact, Bergens observed a related product in the reaction between a lactone and an octahedral trans-[Ru(H)2(Binap)(diamine)] complex at −80 °C.30 Formation of 2-Ru-HemAc from the ester in Figure 3 is equivalent to carbonyl group insertion into a Ru−H bond, and its reverse is a β-hydride elimination. Related insertions are known for ketones31,32 and CO2.13,33 Similarly, a β-H elimination was recently observed in an octahedral Ru− ethanoxide at near −30 °C (thus mediating alcohol dehydrogenation).34 By analogy with the familiar hydride reactions, Figure 3 defines a pair of new insertion and elimination reactions involving the alkoxide group. Interestingly, the barrier for direct slippage from 3-IP-H to 2-RuHemAc is calculated to be high (9.1 kcal/mol). In contrast, ΔHo⧧ from 3-IP-OR to 2-Ru-HemAc is only 2.8 kcal/mol, providing thereby an accessible route to 2-Ru-HemAc. Thus, ion-pair formation and rearrangement can in principle mediate interconversion among the species in Figure 3 from all directions. A facile metathesis would require a balance in the energy of three TSs. Path a1 in Figure 1 affords slightly lower energy B
dx.doi.org/10.1021/om400122n | Organometallics XXXX, XXX, XXX−XXX
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the TSs for proton transfer from the ligand to the hemiacetal oxide past hydride transfer along paths b1 and b2 to be 13.2 and 15.0 kcal/mol, respectively, significantly higher than the slippage TSs on paths a1 and a2 (10.7 and 11.6 kcal/mol). This prediction is not changed when the density functional or the ECP used in the calculations is changed (Table S2, Supporting Information) or when the calculations are done on the diethylamine complex (1-Ru-H; eq 1). Nevertheless, given the very different natures of the proton transfer and slippage TSs and the simplistic solvent model applied in the calculations, computed energy differences of this magnitude may be too small to eliminate the role of the hemiacetal in catalysis. Note, however, that for ester hydrogenation to be completed, a hemiacetal intermediate will have to fragment into an aldehyde and an alcohol. The metathesis in Figure 2 is striking in that it achieves both carbonyl reduction and C−OR bond cleavage in a most straightforward manner. Figure 2 predicts a lack of an electronic barrier for alkoxide transfer from 2-Ru-OMe to acetaldehyde. If this is the case, we reasoned that alkoxide transfer could take place with other carbonyl compounds, and this could lead to new metatheses, such as an OR/OR′ exchange between a Ru−alkoxide and an ester. To explore this possibility, we computed the analogues of all the species in Figure 2 starting with 2-Ru-OMe in place of 2Ru-H. To our surprise, and as specified in Figure 4, the barrier
hydride transfer and slippage TSs (5.8 and 10.7 kcal/mol, respectively) than path a2 discussed in Figure 2, but due to a flat PES in the direction of C−OMe cleavage, we could obtain only an approximate Horel of 7.2 kcal/mol for the C−OR cleavage TS.35 On the other hand, Horel values of TS slip along paths b1 and b2 are ca. 3 kcal/mol higher than for path a2. These results implicate subtle interaction modes between the hemiacetaloxide and the cationic fragment that are dependent on the stereoisomeric details defined by the asymmetric PNN ligand. The metathesis in Figure 2 can obviously have implications for catalysis. Although the step itself is calculated to be endoergic by 8.4 kcal/mol in the hydrogenation direction, catalytic hydrogenation of the aldehyde product by a separate 2-Ru-H molecule (which should be abundant under hydrogenation conditions) is exoergic and is expected to be fast;36 thus, it should drive full ester hydrogenation. In applying Figure 2 to alcohol dehydrogenative coupling, we first note that addition of few equivalents of methanol to 1-Ru in toluene at room temperature yields 1-Ru-OMe rapidly and quantitatively.4 Our calculations of methanol addition to 2-Ru in eq 5 afford ΔGorxn = −2.9 kcal/mol, only slightly less exoergic than H2 addition to 2-Ru in eq 6 (−5.3 kcal/mol).
Thus, under the conditions of the coupling experiment (which typically include reflux to expel H2) 2-Ru-OMe should be abundant. 2-Ru-OMe can undergo a β-hydride elimination to give an aldehyde and 2-Ru-H (Figure 3).32 Once the aldehyde is produced, a highly exoergic coupling metathesis into the ester and 2-Ru-H can proceed by “alkoxide transfer” from another 2-Ru-OMe followed by slippage and hydride transfer. The calculated Horel and Gorel values of 3-TS-slip in Figure 2 are only 3.4 and 11.1 kcal/mol, respectively, above the separated aldehyde and 2-Ru-OMe; thus, even small concentrations of these two species would suffice for the metathesis route to be relevant in coupling catalysis. Note that 1-Ru does catalyze ester formation quantitatively starting with aldehyde− alcohol mixtures.6 Completion of catalytic cycles from Figure 2 will depend on the regeneration of 2-Ru-H from 2-Ru-OMe and H2 or the regeneration of 2-Ru-OMe from 2-Ru-H and MeOH. These reactions can take place dissociatively via the bifunctional equations (5) and (6) or by solvent assisted37 and direct hydrogenolysis routes.29,38 Addressing the question of the ratelimiting step in catalysis is not an objective of the present study. The point here is that a metathesis would lead to a simple scheme that gives similar roles for the observed 2-Ru-H and 2Ru-OMe complexes in catalysis, as summarized in eq 7.
Figure 4. TSs and minima for OR/OR′ metathesis between 3 and 2Ru-OMe. Values are given in kcal/mol relative to the separated reactants.
for the metal to carbonyl alkoxide transfer step as well as that for subsequent slippage came out to be similar to those of their H/OR counterparts in Figure 2. For implications, we consider yet another notable reaction from the Milstein group (eq 8).39 This time 1-Ru catalyzes under neutral conditions the acylation of two secondary alcohol molecules (R″OH) using one symmetrical ester (RCOOCH 2 R) and releases two H 2 molecules.
All it would take to account for this transesterification is to begin with alcohol addition to 1-Ru to obtain two octahedral 1Ru-OR″ intermediates. By Figure 4, production of the first mixed ester along with the new octahedral 1-Ru-OCH2R would follow by an OR″/OCH2R metathesis between 1-Ru-OR″ and the symmetrical ester. An ion-pair-mediated β-hydride
In comparing the energetics of the metathesis and the hemiacetal hydrogenation paths, we calculated Horel values for C
dx.doi.org/10.1021/om400122n | Organometallics XXXX, XXX, XXX−XXX
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(9) Gunanathan, C.; Milstein, D. Top. Organomet. Chem. 2011, 37, 55. (10) Ghosh, S. C.; Muthaiah, S.; Zhang, Y.; Xu, X.; Hong, S. H Adv. Synth. Catal. 2009, 351, 2643. (11) Zeng, H.; Guan, Z. J. Am. Chem. Soc. 2011, 133, 1159. (12) Gnanaprakasam, B.; Balaraman, E.; Gunanathan, C.; Milstein, D. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 1755. (13) Langer, R.; Diskin-Posner, Y.; Leitus, G.; Shimon, L. J. W.; BenDavid, Y.; Milstein, D. Angew. Chem., Int. Ed. 2011, 50, 9948. (14) Balaraman, E.; Fogler, E.; Milstein, D. Chem. Commun. 2012, 48, 1111. (15) Nielsen, M.; Junge, H.; Kammer, A.; Beller, M. Angew. Chem., Int. Ed. 2012, 51, 5711. (16) Li, W.; Xie, J.-H.; Lin, H.; Zhou, Q.-L. Green Chem. 2012, 14, 2388. (17) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P. Angew. Chem., Int. Ed. 2007, 46, 7473. (18) Zweifel, T.; Naubron, J-V; Grützmacher, H. Angew. Chem., Int. Ed. 2009, 48, 559. (19) Ito, M.; Koo, L.-W.; Himizu, A.; Kobayashi, C.; Sakaguchi, A.; Ikariya, T. Angew. Chem., Int. Ed. 2009, 48, 1324. (20) (a) O, W. W. N.; Lough, A. J.; Morris, R. H. Chem. Commun. 2010, 46, 8240. (b) O, W. W. N.; Morris, R. H. ACS Catal. 2013, 3, 32. (21) Ito, M.; Ootsuka, T.; Watari, R.; Shiibashi, A.; Himizu, A.; Ikariya, T. J. Am. Chem. Soc. 2011, 133, 4240. (22) John, J. M.; Bergens, S. H. Angew. Chem., Int. Ed. 2011, 50, 10377. (23) Sun, Y.; Koehler, C.; Tan, R.; Annibale, V. T.; Song, D. Chem. Commun. 2011, 47, 8349. (24) Spasyuk, D.; Smith, S.; Gusev, D. G. Angew. Chem., Int. Ed. 2012, 51, 2772. (25) Dub, P. A.; Ikariya, T. ACS Catal. 2012, 2, 1718. (26) Prechtl, M. H. G.; Wobser, K.; Theyssen, N.; Ben-David, Y.; Milstein, D.; Leitner, W. Catal. Sci. Technol. 2012, 2, 203. (27) Li, H.; Wang, X.; Huang, F.; Lu, G.; Jiang, J.; Wang, Z.-X. Organometallics 2011, 30, 5233. (28) Hasanayn, F.; Abu-El-Ez, D. Inorg. Chem. 2010, 49, 9162. (29) Hasanayn, F.; Morris, R. H. Inorg. Chem. 2012, 51, 10808. (30) Takebayashi, S.; Bergens, S. H. Organometallics 2009, 28, 2349. (31) Takebayashi, S.; Dabral, N.; Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2011, 133, 9666. (32) Spasyuk, D.; Gusev, D. G. Organometallics 2012, 31, 5239. (33) Schmeier, T. J.; Dobereiner, G. E.; Crabtree, R. H.; Hazari, N. J. Am. Chem. Soc. 2011, 133, 9274. (34) Montag, M.; Zhang, J.; Milstein, D. J. Am. Chem. Soc. 2012, 134, 10325. (35) Attempts to locate IP-OR and TS-OR along path a1 encountered convergence problems. To allow for comparison with path a2, the two points were calculated by conducting geometry minimization with the C−O and Ru−OMe bond distances fixed at the respective values of the two species from path a2. The given features of the PES imply that, once TS slippage is crossed, C−OR breakage is essentially complete. (36) We calculate the enthalpies of the TSs of sequential hydride and proton transfer from 2-Ru-H to acetaldehyde to be −1.1 and −0.3 kcal/mol, respectively (relative to the separated reactants). (37) Iron, M. A.; Ben-Ari, E.; Cohen, R.; Milstein, D. Dalton Trans. 2009, 9433. (38) Yang, X. Inorg. Chem. 2011, 50, 12836. (39) Gnanaprakasam, B.; Ben-David, Y.; Milstein, D. Adv. Synth. Catal. 2010, 352, 3169. (40) Khaskin, E.; Iron, M. A.; Shimon, L. J. W.; Zhang, J.; Milstein, D. J. Am. Chem. Soc. 2010, 132, 8542. (41) Gnanaprakasam, B.; Milstein, D. J. Am. Chem. Soc. 2011, 133, 1682.
elimination from 1-Ru-OCH2R along the path included in Figure 3 would produce an aldehyde and 1-Ru-H. By Figure 2, a (cross) H/OR metathesis between the aldehyde and the second 1-Ru-OR″ would yield the second mixed ester and another 1-Ru-H. By eq 7, H2 release and the start of a new reaction cycle can proceed by reaction between R″OH and 1Ru-H. In this context we note that, as is the case with alcohols, amines also undergo metal−ligand cooperative N−H addition to analogues of 1-Ru to give octahedral Ru−amides (1-RuNHR).1,40 Accordingly, it is possible to envisage a cross H/ NHR metathesis in the hydrogenation of carboxamides and in the dehydrogenative coupling between amines and alcohols (eq 3 in both directions). Likewise, the discovery that 1-Ru catalyzes carboxamide formation from esters and amines (eq 9)41 can be rationalized straightforwardly by an N−H bond addition to 1-Ru followed by a cross NHR/OR metathesis with the ester.
Thus, accepting the new metal/acyl metathesis mode identified by the calculations in the present work leads to one simple reaction model systematically applicable to all aspects of Milstein’s extraordinary hydrogenation, dehydrogenative coupling, and cross coupling chemistry. A metathesis mechanism suggests a distinct strategy in catalyst design.
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ASSOCIATED CONTENT
S Supporting Information *
Text and tables giving computational details and data for Figures 2 and 3. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail for F.H.:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by the Lebanese National Council for Scientific Research. F.H. thanks Prof. R. H. Morris for hosting a Visiting Professorship at the University of Toronto. TAMUQatar is thanked for providing computational resources. This study is dedicated to Professor Ronald Christensen on the occasion of his retirement from Bowdoin College.
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REFERENCES
(1) Gunanathan, C.; Milstein, D. Acc. Chem. Res. 2011, 44, 588. (2) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2006, 45, 1113. (3) Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W.; Milstein, D. J. Am. Chem. Soc. 2010, 132, 16756. (4) Balaraman, E.; Gunanathan, C.; Zhang, J.; Shimon, L. J. W.; Milstein, D. Nat. Chem. 2011, 3, 609. (5) Balaraman, E.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2011, 50, 11702. (6) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840. (7) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317, 790. (8) Milstein, D. Top. Catal. 2010, 53, 915. D
dx.doi.org/10.1021/om400122n | Organometallics XXXX, XXX, XXX−XXX
