D Exchange of Unactivated Aliphatic C–H Bonds

Article pubs.acs.org/Organometallics

Catalytic H/D Exchange of Unactivated Aliphatic C−H Bonds Sun Hwa Lee, Serge I. Gorelsky,* and Georgii I. Nikonov* Chemistry Department, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada S Supporting Information *

ABSTRACT: Complex Cp(iPr3P)RuH3 (1) catalyzes H/D exchange between a variety of organic substrates and C6D6 or D2O, including aliphatic groups. Experimental data show the preference in activation of methyl groups versus benzylic positions. Methylene positions react only if the substrate contains a functional group (arene, halogen, O- or N-based groups). DFT calculations were used for the model complex Cp(Me3P)RuH3 (2) to study the mechanism of C−H bond activation.

■

INTRODUCTION Catalytic H/D exchange is of great importance as a method of preparing D-labeled compounds1−3 and as an important mechanistic tool to study the activation of C−H bonds.4−8 D-Labeling of C−H acidic substrates, such as chloroform and acetone, is very well established.1b,9 H/D exchange in arenes is also well known and is believed to proceed via a sequence of C−H oxidative addition/reductive elimination steps or to involve C−H activation on polar metal−heteroatom bonds.4a,7b,10 Deuteration of olefins has several precedents and may involve the conventional olefin insertion/β-H elimination mechanism.11 In contrast, H/D exchange in aliphatic substrates is still poorly studied. Although, Pt-catalyzed D-transfer from D2O to alkanes was reported nearly four decades ago,12,13 only a few examples of catalytic deuteration of aliphatic substrates are known,14 and these are usually limited to reactive allylic and benzylic positions.9,15 The most prominent manifestations of H/D exchange in alkanes, including methane, and in alkyl chains of organic substrates have been achieved on the cationic system [Cp*LIrX]+ (L= PMe3 on NHC-carbene), which operates by means of electrophilic C−H activation.5b,16 Understanding factors that govern the selectivity in C−H bond activation is essential for the design of tailored catalysts for alkane functionalization. Earlier studies suggested that in the absence of directing groups the initial C−H activation in alkanes is kinetically not very selective.4b,6i However, C−H bond activation in alkanes on Rh complexes shows strong preference for the terminal positions,17 which may be related to the increased strength of the M−C(1°) bond versus the M− C(2°) bonds, which in turn relates to the better stabilization of the carboanionic character.18 Similarly, the preferred activation of more acidic CH positions is observed in borylation of aromatic substrates.19 Here we report deuteration of organic substrates mediated by a Ru complex, which (i) shows selectivity for the activation of terminal alkane positions, (ii) uses D2O as a cheap source of deuterium, (iii) highlights the © 2013 American Chemical Society

need of initial anchoring of the substrate to the complex as a prerequisite for successful C−H bond activation, but (iv) does not show any correlation with the C−H acidity. Functional group directed C−H activation in arenes and olefins is being intensively used in organic synthesis,20 but is less known for the activation of alkyl groups.21

■

RESULTS AND DISCUSSION Catalytic H/D Exchange. Our initial observation was that heating a solution of Cp(iPr3P)RuH3 (1) in C6D6 at 100 °C results in disappearance of the Cp signal in the 1H NMR spectrum followed by disappearance of the PCH signals and then the PCDCH3 signals, accompanied by an increase of the residual C6D5H signal. 31P NMR confirmed the integrity of the complex, whereas 2H NMR established the deuteration of all CH positions in 1. Whereas C−H activation in the Cp and PCH positions has many precedents,22 the H/D exchange in the methyl groups of 1 prompted the possibility of an intermolecular pathway. A variety of substrates were then screened in catalytic H/D exchange with C6D6 mediated by 1 (5%) (Scheme 1). In the case of alkylbenzenes (entries a−e), deuteration of the ring occurs fast followed by slower reactions in the alkyl groups. We were surprised to notice that the terminal positions are deuterated faster than the internal ones, even faster than the usually more reactive benzylic positions (entries b−e). In the case of 1-phenylbutane (entry d), of all the aliphatic positions only the remote δ-position was engaged in exchange. These observations contradict the expectation that more acidic (in this case benzylic5a) positions should react faster. When hexane and decane were tried as substrates (entries m and n), H/D scrambling occurs only in the methyl groups, whereas cyclohexane (entry o) stays unreacted even Received: September 19, 2013 Published: October 9, 2013 6599

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604

Organometallics

Article

and the lack of deuteration of methylenes of cyclohexane (entry o) and cyclooctane (p). In contrast, comparable deuterium incorporation in both the primary and secondary CH positions of aliphatic nitriles takes places, regardless of the lengths of the alkyl chain and the CH acidity (Scheme 1, entries r−u). But most surprisingly, we did observe D scrambling into the CH and CH2 groups of methylcyclohexane (entry q)!25 The above results suggest that H/D exchange in alkyl chains happens only for substrates featuring potentially donating functionalities (arene π system, CC double bond, O- and N-donors) or the CH3 group. Whereas preferred H/D scrambling in the aromatic (Scheme 1, entries a−e) and vinylic positions is expected and can be explained in terms of sp2 hybridization, the comparable activation of the activated α- and nonactivated β-positions of THF (entry f) and the preferred exchange in the β-position of Et2O (entry g) speak against the CH acidity as a prerequisite for CH bond activation. The exclusive deuteration of the heteroaromatic core of alkyl thiophenes and furanes is in sharp contrast with deuterium scrambling into the alkyl chain of alkylbenzenes. We attribute this difference to the better donating ability of heteroaromatics and their stronger coordination to the catalyst. We then studied H/D exchange in D2O as a cheaper deuterium source. The substrates screened were limited to those that show significant solubility in water (Scheme 2).

Scheme 1. Catalytic H/D Exchange of Substrates Using C6D6 as the Deuterium Source and 1 as the Catalyst (5 mol %)a

Scheme 2. Catalytic H/D Exchange Using D2O as the Deuterium Source and 1 as the Catalysta

T = 100 °C; reaction time: 6 days (a, e), 33 days (b), 15 days (c), 10 days (d, n, p), 9 days (q), 1 day (f, j, k), 5 days (g), 4 days (r−u), 3 days (h, i, l, m). Conditions for o: 15% of 1 for 18 days, 100 °C. The reactions were terminated at arbitrary times, which do not correspond to complete catalyst deactivation.

a

after extended heating at 100 °C. Deuteration of ethers goes easily, with the remarkable selective deuteration of the less acidic β-position in Et2O (entry g). Even the remote and unactivated tBu group of tBuOMe is engaged in exchange (entry h). In contrast, in the case of alkyl-substituted heteroaromatics, only exclusive deuteration of the ring was observed, without any deuterium scrambling into alkyl chains (entries i−k). With 1-hexene as a substrate, we initially observed isomerization into 2-hexene followed by the H/D exchange in the vinylic and alkyl positions (entry l). Attempted deuteration of styrene resulted in the catalyst deactivation by means of formation of the complex Cp(iPr3P)RuH(styrene)23 accompanied by evolution of an equivalent of ethylbenzene. Previously, kinetic modeling on competitive CH activation of propane and pentane by a Rh complex suggested that secondary CH bonds coordinate to metal ∼1.5 times faster than methyl groups, but C−H oxidative cleavage occurs much faster on the primary CH bonds.17a In the case of nitrile activation, this fact accounts for the strong kinetic preference of methyl group activation versus the thermodynamically preferable activation of the α-CH2 groups of nitriles.24 We observed a similar preference for the H/D exchange in the methyl groups of linear alkanes (Scheme 1, entries m and n)

a

Reaction conditions (under nitrogen): 1 (5 mol %), substrates (0.3 mmol), D2O (0.5−0.7 mL), T = 100 °C. The reactions were terminated at arbitrary times, which do not correspond to complete catalyst deactivation.

Again, aromatic compounds react easily, and the α- and βpositions of THF are equally reactive. Cyclohexanone, ether, and iPrCN react preferably at the α-CH bond, which may indicate a concurrent acid-catalyzed exchange. Apart from the reactions of C−H acidic substrates such as cyclohexanone in polar media (D2O), there is little correlation between the C−H acidity and the extent of deuteration. This observation is reminiscent of the selective activation of primary CH bonds of alkylnitriles on the fragment Tp(L)Rh24 and is in contrast with the C−H activation on Gunnoe’s system Tp(L)RuX, which proceeds as an intramolecular proton transfer and correlates with the acidity of substrate R−H and the basicity of group X (X = Me, OH, NHR′).21a This difference in reactivity likely reflects the difference in electrondonating ability of the Cp vs Tp ligands and hence the increased electrophilicity of Gunnoe’s system. DFT Studies. The H/D exchange catalyzed by complex Cp(R3P)RuH3 can be explained, at least in principle, by the 6600

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604

Organometallics

Article

mechanism shown in Scheme 3 using benzene as an example. Heating a C6D6 solution of 1 results in dehydrogenation of the Scheme 3. Possible Mechanistic Pathway for the H/D Exchange between C6D6 and Cp(iPr3P)RuH3 (1)

Figure 1. Calculated Gibbs free energies (kcal mol−1) for C−H bond cleavage via pathways I and II with 2 as the catalyst at the B3LYP level of theory (at 298 K in the gas phase) and the C−H bond cleavage transition states for both pathways. The relevant C−H, Ru−H, and Ru−C bond lengths (Å) for these transition states are shown.

starting compound to give an intermediate Ru monohydride complex. The next step involves coordination of the C−D bond followed by oxidative addition of the C−D bond of C6D6 to give a Ru phenyl derivative. The reductive elimination of C6DxH6−x results in a Ru monodeuterium complex. In the presence of a substrate, this sequence in CH activation is repeated to give finally the deuterated product. The key difference between the Cp(iPr3P)Ru fragment and the related Tp(Me3P)Ru fragment is that the former is more electron rich and can stabilize the formal oxidation state RuIV, such as in Cp(iPr3P)Ru(H)(R)(D), whereas C−H activation in Gunnoe’s complex goes via a formal RuII σ-complex Tp(Me3P)Ru(η2R′H)(X).21 To understand better the mechanism of sp3 C−H bond activation, density functional theory (DFT) calculations were performed with three exchange−correlation (XC) functionals (B3LYP,26 M06L,27 and PBE28) for the model complex Cp(Me3P)RuH3 (2). The M06L and PBE functionals were selected to assess the validity of reaction energies calculated with the default level of DFT (B3LYP calculations). Since the results obtained by using the PBE and M06L functionals are similar to calculations with the B3LYP functional (Figures S1 and S2),29 we will focus our discussion on the latter. We considered two main scenarios of catalyst activation: dissociation of dihydrogen from 2 and dissociation of the phosphine ligand. The latter turned out to be a higher energy process (see below). Several reaction pathways were considered using CH4 as a model substrate. The two lowest energy pathways are shown in Figure 1. The pathway I corresponds to oxidative addition of the C−H bond to RuII and results in formation of a symmetric RuIV product, Cp(Me3P)RuH2(R), with the R group in between two hydride ligands. On the other hand, pathway II produces a nonsymmetric product, Cp(Me3P)Ru(H2)(R), with the R group next to the dihydrogen ligand (see below). Both pathway I and pathway II start with the formation of a lowenergy dihydrogen RuII complex, Cp(Me3P)RuH(H2) (1.7 kcal mol−1), and then a high-energy Ru-monohydride intermediate (ΔG298K of 17.2 kcal mol−1). As a first step along the reaction pathways, a weak complex between the substrate and the Rumonohydride is formed. This complex features a three-center Ru···CH agostic interaction,30 which can be characterized by

the value of a three-center bond order31 between the corresponding atoms. The value of the three-center Ru···CH bond order calculated in these complexes (0.09) is 30% of the maximum theoretically possible value for three-center orbital interactions (8/27 or ∼0.296).32 The C−H bond participating in the agostic interaction with the Ru atom is elongated (dC−H = 1.12 Å compared to 1.086−1.089 Å for the other aliphatic C−H bonds), but the Ru−CCH4 distance is still fairly long (2.72 Å), indicating a weak interaction. Afterward, the reaction moves toward the cleavage of the C−H bond via the oxidative transition states TSI for pathway I and TSII for pathway II (Figure 1), having a ΔG⧧298K of 34.5 kcal mol−1 and a ΔG⧧298K of 33.6 kcal mol−1, respectively. The B3LYP functional gives the highest ΔG⧧ values, while the PBE and M06L functionals give ΔG⧧ values that are ∼3 kcal mol−1 lower than those from the B3LYP calculations (Figures S1 and S2). The energies of the calculated barriers for pathways I and II using the three XC functionals are fairly close to each other and do not allow us to rule out one mechanism at the expense of the other. Moreover, the calculated activation barriers for substrates other than CH4 (see below) indicate that the reaction may switch from one pathway to another. Changing temperature from 25 °C to 100 °C affects the barriers for the C−H bond oxidative addition of CH4 only slightly: the ΔG⧧ increases by 0.5 kcal mol−1 for both pathways I and II, Table 1. For pathway I, C−H bond cleavage leads to a RuIV intermediate, Cp(Me3P)RuH2(R), having the R group between two hydride ligands. The internuclear distance between the carbon of the CH3 group and the hydride ligand is 2.21 Å. For pathway II, the intermediate has a short internuclear H−H distance of 0.91 Å and the Mayer bond order33 is 0.59 for the H−H interaction in this structure. Thus, this intermediate is more accurately described as a RuIIdihydrogen complex, Cp(Me3P)Ru(H2)(R), rather than a RuIVdihydride complex. There is also a three-center Ru···HH interaction with a three-center bond order of 0.08 in this intermediate. The TS structure corresponding to the rotation of the H2 ligand in the latter species (Figure S2) has an even 6601

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604

Organometallics

Article

ΔG⧧ value reaches 37.3 kcal mol−1, indicating the least reactive of methyl groups in this series. The calculated barriers for secondary C−H bonds are even higher than for primary C−H bonds, with the lowest ΔG⧧ values being in the 39−40 kcal mol−1 range. However, we found that the C−H bonds of cyclohexane are as robust as the methylene positions of methylcyclohexane. Therefore, this mechanistic model can explain the selectivity for primary vs secondary bond activation but fails to rationalize the occurrence of H/D exchange in methylcyclohexane and the absence of exchange in cyclohexane. In summary, Cp(iPr3P)RuH3 (1) catalyzes H/D exchange of C6D6 and D2O with various substrates, including alkyl groups, with the preferential deuteration of methyl groups over activated positions, such as benzylic positions or the α-CH2 moiety in ether. Methylene and methine positions of alkyl chains are engaged in exchange only if the substrate has a weakly donating functionality (such as arene). For substrates with stronger donating groups (such as heteroarenes) only sp2 C−H bond activation was observed.

Table 1. Calculated Gibbs Free Energies (kcal mol−1) for C− H Bond Cleavage via Pathways I and II with 2 as the Catalyst at the B3LYP Level of Theory (in the gas phase at 298 K unless stated otherwise) sp3 C−H substrate

ΔG(TSI)

ΔG(TSII)

CH4 CH3CH3 C6H5CH3 CH3CH2CH3 C6H5CH2CH3 CH3−C6H11b CH3−C6H11b cyclohexane, C6H12

34.5 (35.0)a 36.0 35.5 39.9 39.3 37.7 39.5eq, 41.7ax 39.5eq, 41.8ax

33.6 (34.1)a 35.7 35.4 41.2 39.8 37.3 41.0eq, 42.4ax 40.8eq, 42.3ax

ΔG at 373 K. bMethylcyclohexane with the methyl group in the equatorial position (the lowest energy conformation). TS structures involving methylcyclohexane with the axial methyl group are higher in energy than the corresponding TS structures involving methylcyclohexane with an equatorial methyl group.

a

shorter H−H bond (0.84 Å), higher Mayer H−H bond order (0.66), and a ΔG⧧ that is slightly lower than for the C−H cleavage transition state TSII. The Ru···HH interaction has a three-center bond order of 0.13 in this structure. Calculations for pathways I and II were repeated using the implicit solvent model to test the influence of solvent on the reaction barriers (Figures S3 and S4). The reaction energies from the calculations with benzene as a solvent are very similar to those from the gas-phase calculations, with the oxidative addition barriers in benzene being 0.8 kcal mol−1 lower than those in the gas phase. When going from benzene to water as a solvent, the oxidative addition barriers for both pathways increase by 3.5 and 5.0 kcal mol−1 for TSI and TSII, respectively. Other oxidative addition pathways, such as a phosphinedissociative pathway (Figure S5), have been investigated. Dissociation of PMe3 from Cp(Me3P)RuH3 to form CpRuH3 requires a ΔG298K of +33.7 kcal mol−1 (+30.7 kcal mol−1 at 100 °C). The high-energy intermediate CpRuH 3 undergoes conversion to the dihydrogen complex CpRuH(H2) (ΔG298K of 32.1 kcal mol−1, ΔG373K of 29.2 kcal mol−1), featuring a short H−H distance of 0.87 Å. The lowest value of the free energy barrier for the oxidative addition of CH4 to the CpRuH(H2) intermediate is prohibitory high (48.8 kcal mol−1, Figure S5). If we consider a pathway with H2 dissociation from CpRuH(H2) and oxidative addition of methane to the CpRu(H) intermediate, the energies of the corresponding species are even higher. The Gibbs free energy of CpRu(H) is 42.3 kcal mol−1 and 37.2 kcal mol−1 at 25 and 100 °C, respectively. The lowest ΔG⧧ value for the oxidative addition of CH4 to the CpRuH intermediate is 55.6 kcal mol−1 (Figure S5). Thus, the oxidative addition pathways with phosphine dissociation, with and without H2 dissociation, are not competitive with the oxidative addition via the Cp(Me3P)RuH intermediate (pathways I and II). All attempts to optimize transition states for C− H bond cleavage using alternative mechanisms (such as σ-bond metathesis or ring slippage) led to the transition-state structures corresponding to the oxidative addition. C−H bond cleavage barriers for several substrates with primary and secondary sp3 C−H bonds are shown Table 1. When going from methane to ethane, the ΔG⧧ increases by 1.5 and 2.1 kcal mol−1 for pathways I and II, respectively. A slightly smaller increase is observed for the Me group of toluene. However, for the Me group of methylcyclohexane, the lowest

■

EXPERIMENTAL DETAILS

■

ASSOCIATED CONTENT

All manipulations were performed using an MBraun glovebox with a nitrogen atmosphere. C6D6 was dried by distillation from K/Na alloy. NMR spectra were obtained with Bruker DPX-300 (1H 300 MHz; 13C 75.5 MHz; 29Si 59.6 MHz) and Bruker DPX-600 (1H 600 MHz; 13C 151 MHz) instruments at room temperature. Cp(iPr3P)RuH3 was prepared according to a literature procedure.34 General Procedure for Catalytic H/D Exchange. All catalytic experiments were done under a nitrogen atmosphere using NMR tubes equipped with Teflon valves and external standard (a sealed capillary with a solution Cp2Fe in C6D6). In a typical procedure, to a mixture of substrate (0.30 mmol) and Cp(iPr3P)RuH3 (0.005 g, 5 mol %) was added the deuterated solvent (C6D6 or D2O). The mixture was heated at 100 °C, and the progress of the reaction was monitored by 1 H and 2H NMR spectroscopy. The extent of deuterium incorporation was calculated by integration of the 1H NMR spectrum against the Cp2Fe standard. The location of deuterium atoms in the product was confirmed by 2H NMR. Computational Details. Density functional theory calculations have been performed, unless noted otherwise, at the B3LYP26 level using the Gaussian 09 package.35 To assess the influence of different DFT treatments on the calculated energies, calculations for the C−H bond activation with CH4 as a substrate were repeated with the PBE28 and M06L27 XC functionals. The structures of all species were optimized using the mixed double/triple-ζ basis set (DZVP36 on Ru and TZVP37 on all other atoms) in the gas phase. For comparison of reaction energies for CH4 as a substrate in the gas phase and in solution, calculations were conducted using optimizations and harmonic frequency calculations in solution (using the SMD38 implicit solvent model with benzene and water as solvents). Tight SCF convergence criteria (10−8 au) were used for all calculations. Harmonic frequency calculations were used to determine the nature of stationary points and Gibbs free energies at 298 K unless stated otherwise. Intrinsic reaction coordinate (IRC)39,40 calculations were used to confirm the reaction pathways through the corresponding oxidative addition transition states. The electronic structure descriptors (such as two- and three-center bond orders) were calculated using the AOMix package.41

S Supporting Information *

Experimental details and additional computational results (including optimized geometries, electronic and Gibbs free energies of relevant structures). This material is available free of charge via the Internet at http://pubs.acs.org. 6602

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604

Organometallics

■

Article

Organometallics 2009, 28, 45. (d) Zhou, J.; Hartwig, J. F. Angew. Chem., Int. Ed. 2008, 47, 5783. (e) Kohl, G.; Rudolph, R.; Pritzkow, H.; Enders, M. Organometallics 2005, 24, 4774. (f) Rybtchinski, B.; Cohen, R.; Ben-David, Y.; Martin, J. M. L.; Milstein, D. J. Am. Chem. Soc. 2003, 125, 11041. (g) Faller, J. W.; Smart, C. J. Organometallics 1989, 8, 602. (h) Lenges, C. P.; White, P. S.; Brookhardt, M. J. Am. Chem. Soc. 1999, 121, 4385. (i) Faller, J. W.; Felkin, H. Organometallics 1985, 4, 1488. (12) (a) Gol’dshleger, N. F.; Tyabin, M. B.; Shilov, A. E.; Shteinman, A. A. Russ. J. Phys. Chem. 1969, 43, 1222. (b) Hodges, R. J.; Webster, D. E.; Wells, P. B. J. Chem. Soc., Chem. Commun. 1971, 462. (c) Tyabin, M. B.; Shilov, A. E.; Shteinman, A. A. Dokl. Akad. Nauk 1971, 198, 380. (13) For related research on arenes, see: (a) Garnet, J. L.; Hodges, R. J. J. Am. Chem. Soc. 1967, 89, 4546. (b) Garnet, J. L.; Hodges, R. J. J. Chem. Soc., Chem. Commun. 1967, 1001. (c) Garnet, J. L.; Hodges, R. J. Aust. J. Chem. 1974, 27, 129. (d) Hodges, R. J.; Garnett, J. L. J. Phys. Chem. 1968, 72, 1673. (14) (a) Jones, W. D.; Maguire, J. A. Organometallics 1986, 5, 590. (b) Rhinehart, J. L.; Manbeck, K. A.; Buzak, S. K.; Lippa, G. M.; Brennessel, W. W.; Goldberg, K. I.; Jones, W. D. Organometallics 2012, 31, 1943. (15) For an example of heterogeneous catalytic H/D exchange, see: Ito, N.; Watahiki, T.; Maesawa, T.; Maegawa, T. Adv. Synth. Catal. 2006, 348, 1025. (16) (a) Golden, J. T.; Andersen, R. A.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 5837. (b) Corderán, R.; Sanaú, M.; Peris, E. J. Am. Chem. Soc. 2006, 128, 3974. (c) Skaddan, M. B.; Yung, C. M.; Bergman, R. G. Org. Lett. 2004, 6, 11. (d) Yung, C. M.; Skaddan, M. B.; Bergman, R. J. Am. Chem. Soc. 2004, 126, 13033. (e) Klei, S. R.; Golden, J. T.; Burger, P.; Bergman, R. G. J. Mol. Catal. A: Chem. 2002, 189, 79. (f) Feng, Y.; Jiang, B.; Boyle, P. A.; Ison, E. A. Organometallics 2010, 29, 2857. (17) (a) Jones, W. D. Inorg. Chem. 2005, 44, 4475. (b) Jones, W. D.; Feher, F. J. Organometallics 1983, 2, 562. (18) Harvey, J. N. Organometallics 2001, 20, 4887. (19) Vanchura, B. A.; Preshlock, S. M.; Roosen, P. C.; Kallepalli, V. A.; Staples, R. J.; Maleczka, R. E.; Singleton, D. A.; Smith, M. R. Chem. Commun. 2010, 46, 7724. (20) (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (c) Paul, S.; Chotana, G. A.; Holmes, D.; Reichle, R. C.; Maleczka, R. E.; Smith, M. R. J. Am. Chem. Soc. 2006, 128, 15552. (d) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (21) (a) Foley, N. A.; Gunnoe, T. B.; Cundari, T. R.; Boyle, P. D.; Petersen, J. L. Angew. Chem., Int. Ed. 2008, 47, 726. (b) Wang, D.-H.; Wasa, M.; Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 7190. (c) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510. (d) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 124, 9542. (e) Simmons, E. M.; Hartwig, J. F. Nature 2012, 483, 70. (22) See, for example: Perthuisot, C.; Fan, M.; Jones, W. D. Organometallics 1992, 11, 3622. (23) See Supporting Information for details. (24) Vetter, A. J.; Rieth, R. D.; Jones, W. D. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 6957. (25) C−H activation at the 2° position has been reported very recently: Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 12422. (26) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785. (27) Zhao, Y.; Truhlar, D. G. J. Chem. Phys. 2006, 125, 194101. (28) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77, 3865. (29) See the Supporting Information for additional details. (30) Brookhart, M.; Green, M. L. H.; Parkin, G. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 6908. (31) (a) Sannigrahi, A. B.; Kar, T. Chem. Phys. Lett. 1990, 173, 569. (b) Kar, T.; Marcos, E. S. Chem. Phys. Lett. 1992, 192, 14. (c) Lafrance, M.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2007, 129, 14570.

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected] Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by a DG NSERC grant to G.I.N. S.I.G. thanks the Centre for Catalysis Research and Innovation (CCRI), University of Ottawa, for supporting this work.

■

REFERENCES

(1) (a) Thomas, A. F. Deuterium Labeling in Organic Chemistry; Meridith Corporation: New York, 1971. (b) Junk, T.; Catallo, W. J. Chem. Soc. Rev. 1997, 26, 401. (c) Atzrodt, J.; Derdau, V.; Fey, T.; Zimmermann, J. Angew. Chem., Int. Ed. 2007, 46, 7744. (2) For the earlier work on heterogeneous H/D exchange, see: (a) Leitch, L. C. Can. J. Chem.-Rev. Can. Chim. 1954, 32, 813. (b) Brown, W. G.; Garnett, J. L. J. Am. Chem. Soc. 1958, 80, 5272. (c) Garnett, J. L.; Sollich, W. A. J. Catal. 1963, 2, 350. (3) For a recent application for preparation of labeled amines, see: Neubert, L.; Michalik, D.; Bähn, S.; Imm, S.; Neumann, H.; Atzrodt, J.; Derdau, V.; Holla, W.; Beller, M. J. Am. Chem. Soc. 2012, 134, 12239− 12244. (4) For mechanistic considerations, see: (a) Lersch, M.; Tilset, M. Chem. Rev. 2005, 105, 2471. (b) Driver, T. G.; Day, M. W.; Labinger, J. A.; Bercaw, J. E. Organometallics 2005, 24, 3644. (5) (a) Prechtl, M. H. G.; Holscher, M.; Ben-David, Y.; Theyssen, N.; Loschen, R.; Milstein, D.; Leitner, W. Angew. Chem., Int. Ed. 2007, 47, 2269. (b) Klei, S. R.; Golden, J. T.; Tilley, T. D.; Bergman, R. G. J. Am. Chem. Soc. 2002, 124, 2092−2093. (c) Iluc, V. M.; Fedorov, A.; Grubbs, R. H. Organometallics 2012, 31, 39. (6) (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b) Lyins, T. W.; Stanford, M. S. Chem. Rev. 2010, 110, 1147. (c) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890. (d) Crabtree, R. H. Dalton Trans. 2003, 3985. (e) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507. (f) Crabtree, R. H. Dalton Trans. 2001, 2437. (g) Stahl, S. S.; Labinger, J. A.; Bercaw, J. E. Angew. Chem., Int. Ed. 1998, 37, 2181. (h) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97, 2879. (i) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc. Chem. Res. 1995, 28, 154. (7) (a) Wei, C. S.; Jimenez-Hoyos, C. A.; Videa, M. F.; Hartwig, J. F.; Hall, M. B. J. Am. Chem. Soc. 2010, 132, 3078. (b) Feng, Y.; Lail, M.; Barakat, K. A.; Cundari, T. R.; Gunnoe, T. B.; Petersen, J. L. J. Am. Chem. Soc. 2005, 127, 14174. (8) For examples of application to Ru catalysis, see: Louillat, M.-L.; Patureau, F. W. Org. Lett. 2013, 15, 164. (9) Erdogan, G.; Grotjahn, D. B. Top. Catal. 2010, 53, 1055. (10) (a) Feng, Y.; Lail, M.; Foley, N. A.; Gunnoe, T. B.; Barakat, K. A.; Cundari, T. R.; Petersen, J. L. J. Am. Chem. Soc. 2006, 128, 7982. (b) Hanson, S. K.; Heinekey, D. M.; Goldberg, K. I. Organometallics 2008, 27, 1454. (c) Derdau, V.; Artzrodt, J.; Zimmermann, J.; Kroll, C.; Brückner, F. Chem.Eur. J. 2009, 15, 10397. (d) Ito, N.; Esaki, H.; Maesawa, T.; Imamiya, E.; Maegawa, T.; Saijiki, H. Bull. Chem. Soc. Jpn. 2008, 81, 278. (e) Equillor, B.; Esteruelas, M. A.; Garcia-Raboso, J.; Oliván, M.; Oñate, E. Organometallics 2009, 28, 3700. (f) Cundari, T. R.; Grimes, T.; Gunnoe, T. B. J. Am. Chem. Soc. 2007, 129, 13172. (g) Hoyt, H. M.; Michael, F. E.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126, 1018. (h) Beck, R.; Shoshani, M.; Johnson, S A. Angew. Chem., Int. Ed. 2012, 51, 11753. (i) Davies, C. J. E.; Lowe, J. P.; Mahon, M. F.; Poulten, R. C.; Whittlesey, M. K. Organometallics 2013, 32, 4927. (11) (a) Tse, S. K. S.; Xue, P.; Lin, Z.; Jia, G. Adv. Synth. Catal. 2010, 352, 1512. (b) Erdogan, G.; Grotjahn, D. B. J. Am. Chem. Soc. 2009, 131, 10354. (c) Esqueda, A. C.; Conejero, S.; Maya, C.; Carmona, E. 6603

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604

Organometallics

Article

(32) Gorelsky, S. I. AOMix software manual; http://www.sg-chem. net/, 2013. (33) Mayer, I. Chem. Phys. Lett. 1983, 97, 270. (34) Osipov, A. L.; Gutsulyak, D. V.; Kuzmina, L. G.; Howard, J. A. K.; Lemenovskii, D. A.; Süss-Fink, G.; Nikonov, G. I. J. Organomet. Chem. 2007, 692, 5081. (35) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; 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.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.02; Gaussian Inc.: Wallingford, CT, 2009. (36) Godbout, N.; Salahub, D. R.; Andzelm, J.; Wimmer, E. Can. J. Chem. 1992, 70, 560. (37) Schafer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100, 5829. (38) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378. (39) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154. (40) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523. (41) (a) Gorelsky, S. I.; Lever, A. B. P. J. Organomet. Chem. 2001, 635, 187. (b) Gorelsky, S. I. AOMix−Software Package for Electronic Structure Analysis, Revision 6.82; http://www.sg-chem.net, Ottawa, ON, 2013.

6604

dx.doi.org/10.1021/om4009372 | Organometallics 2013, 32, 6599−6604