Mechanistic Study on the Ruthenium-Catalyzed Direct Amination of

Mar 17, 2014 - Xuan Ye , Philipp N. Plessow , Marion K. Brinks , Mathias Schelwies , Thomas Schaub , Frank Rominger , Rocco Paciello , Michael Limbach...
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Mechanistic Study on the Ruthenium-Catalyzed Direct Amination of Alcohols Dennis Pingen,† Martin Lutz,‡ and Dieter Vogt*,† †

School of Chemistry, University of Edinburgh, King’s Buildings, Joseph Black Building, West Mains Road, Edinburgh EH9 3JJ, Scotland, U.K. ‡ Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands S Supporting Information *

ABSTRACT: The Ru-catalyzed direct amination of alcohols with ammonia was investigated for the RuHCl(CO)(PPh3)3/Xantphos system in order to gain mechanistic insight. For several Ru(II) precursor complexes the influence of different additives on catalytic performance was investigated. NMR studies revealed that the reaction of RuHCl(CO)(PPh3)3/Xantphos with the alcohol in the presence of a strong base initially formed an inactive dihydrido Ru species. However, by addition of a ketone, the dihydride was (re)activated, where the corresponding imine is the actual activator, formed by immediate condensation of the ketone with ammonia. In the absence of a base, added ketone significantly enhanced catalyst activity. Catalytically inactive RuCl2(PPh3)3 could be activated by base, demonstrating that also complexes without the CO ligand give active catalysts. On the basis of these observations a mechanism was proposed, closely related to known transfer hydrogenation mechanisms.

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alcohols, diols, and even ester- and amide-functionalized alcohols (Scheme 2).6b

Scheme 1. “Hydrogen Shuttling” Concept

Scheme 2. RuHCl(CO)(PPh3)3/Xantphos -Catalyzed Direct Amination of Alcohols6b

INTRODUCTION The direct synthesis of amines from alcohols via “hydrogen shuttling” (Scheme 1),1 also called “borrowing hydrogen”2 and

The study presented here especially addresses the steps initializing catalysis and the influence of different additives (base and ketone) on catalyst performance. Cyclohexanol was used as the model substrate for a secondary alcohol throughout this study. Using different Ru(II) precursors, reaction profiles were recorded with and without additive(s) and the involved Ru species studied and identified by NMR. The combined data lead to new mechanistic insights that should prove valuable for further progress in this field.

“hydrogen autotransfer”,3 has recently received much attention.4 Amines are very versatile building blocks for a range of intermediates, polymers, and fine chemicals and therefore are also desired to be derived from biomass. Especially, the direct conversion of alcohols to primary amines using NH3 is highly wanted.4 At present only a few examples of homogeneously catalyzed reactions have been shown to convert alcohols efficiently to primary amines in that way.1,5−7 It is now very important to gain mechanistic insight into this catalytic transformation in order to improve catalyst performance. In addition to increasing catalyst activity and total turnover number it would be desirable to lower the reaction temperature, potentially allowing for asymmetric amination reactions as well. Recently the combination of RuHCl(CO)(PPh3)3 and Xantphos was reported to provide a catalyst that showed high selectivity for primary alcohols, secondary © 2014 American Chemical Society

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RESULTS AND DISCUSSION Catalytic Activity and Initiation. Figure 1 shows the reaction profile for the amination of cyclohexanol with ammonia at 150 °C for the RuHCl(CO)(PPh3)3/Xantphos (1) system. After a short initiation phase the reaction takes off Received: December 13, 2013 Published: March 17, 2014 1623

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Figure 1. Reaction profile for the amination of cyclohexanol with RuHCl(CO)(PPh3)3/Xantphos (1 mol %, 1/1): (■) cyclohexanol; (●) cyclohexylamine; (▲) dicyclohexylimine; (▼) cyclohexylimine, (◆) cyclohexanone. Conditions: 5 mmol of cyclohexanol, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

Figure 3. Low-temperature 31P{1H} NMR spectrum of RuHCl(CO)(PPh3)3/Xantphos (complex 1) after refluxing for 12 h (toluene-d8, 202 MHz, 223 K, δ in ppm): 39.1 (dd, JPP = 14 Hz, JPP = 307 Hz), 35.9 (dd, JPP = 14 Hz, JPP = 301 Hz), 32.9 (dd, JPP = 14 Hz, JPP = 307 Hz), 26.7 (dd, JPP = 14 Hz, JPP = 301 Hz), 20.6 (t, JPP = 14 Hz), 4.2 (t, JPP = 14 Hz).

and goes to completion within 30 h. In order to study the coordination behavior of this system, RuHCl(CO)(PPh3)3 was reacted with 1 equiv of Xantphos. The 1H NMR spectrum showed a broad pseudo doublet of triplets in the hydride region at room temperature (Figure 2, left). However, at low

indicating the similarity of the complexes. Therefore, it is most likely that this is an effect of the fluxionality of the ligand. From this mixture we were able to grow crystals suitable for single-crystal X-ray diffraction. Figure 4 shows the structure of

Figure 2. Hydride region of RuHCl(CO)(PPh3)3/Xantphos (complex 1) after 3 h reflux: (left; d8-toluene, 500 MHz, 298 K) δ −6.8 (ddd, JHP = 24.8 Hz, JHP = 27.2 Hz, JHP = 114.4 Hz); (right; d8-toluene, 500 MHz, 223 K) δ −6.71 (ddd, JHP = 23 Hz, JHP = 31 Hz, JHP = 117 Hz), −7.02 (ddd, JHP = 21 Hz, JHP = 31 Hz, JHP = 110 Hz).

Figure 4. Molecular structure of RuHCl(CO)(PPh3)(Xantphos) (complex 1) in the crystal.8 Displacement ellipsoids are displayed at the 50% probability level. Only the major disorder component is shown. A cocrystallized benzene solvent molecule is omitted for clarity. Selected bond lengths (Å) and angles (deg) with standard uncertainties in parentheses: Ru(1)−H(1) = 1.55(2), Ru(1)−P(1) = 2.3786(5), Ru(1)−P(2) = 2.4993(5), Ru(1)−P(3) = 2.3741(4); P(1)−Ru(1)−P(2) = 98.307(16), P(2)−Ru(1)−P(3) = 106.987(17), P(1)−Ru(1)−P(3) = 153.823(16), H(1)−Ru−P(2) = 178.3(9).

temperature (223 K) this turned into two doublets of doublets of doublets (Figure 2, right). Coupling constants indicate that all the P atoms in the system are magnetically inequivalent. The larger splittings (110 and 117 Hz) belong to a trans P−H coupling, whereas the smaller coupling constants (20−30 Hz) both belong to the cis P−H couplings (Figure 2, right). The splitting pattern and coupling constants are consistent with the formation of RuHCl(CO)(PPh3)(Xantphos), in which Xantphos is coordinated in a cis fashion. The two sets of doublets of doublets of doublets are most likely due to the presence of two conformers in solution. The two conformers are also apparent from the 31P spectrum, in which two sets of P shifts can be found (Figure 3). One set consists of two doublet of doublets with a large trans coupling of 301 Hz and a small coupling of 14 Hz. This is accompanied by a triplet with a coupling constant of 14 Hz. The second set shows the same pattern, though with different shifts, and only a slightly different coupling constant (307 Hz),

RuHCl(CO)(PPh3)(Xantphos) in the crystal. The structure resembles a distorted octahedron which is present as a mixture of two conformers with substitutional disorder between CO and Cl. The crystal structure confirms a cis coordination of Xantphos in the complex. The catalytic reaction is expected to follow the “hydrogen shuttling” sequence. As the first step will be the dehydrogenation of the alcohol, a coordinatively unsaturated species has to be generated to take up the hydrogen.9−11 It is reasonable to assume that the coordinated PPh3 dissociates from the complex under the reaction conditions (150 °C). To prove this, we conducted experiments with varying amounts of PPh3. The turnover frequency linearly correlates with the amount of PPh3 present.12,13 We propose that the alcohol subsequently 1624

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coordinates to the Ru, which activates the O−H bond. While the alcohol itself is not sufficiently acidic, upon coordination it is more likely that it can be deprotonated by NH3. Upon liberation of NH4Cl a Ru alkoxide species would be formed. By β-H elimination from the alkoxide, a Ru dihydride (complex 2) is generated and ketone is liberated (Scheme 3).

Scheme 4. Equilibria Involved in the Direct Amination of Cyclohexanol using Ammonia

Scheme 3. Activation of RuHCl(CO)(PPh3)(Xantphos) Assisted by NH3

will considerably hamper the amine production and regeneration of the active Ru species to start a new cycle. Our consideration now was that, apart from increasing the catalyst concentration (many reports on related reactions use a high catalyst loading), increasing the steady-state concentration of the imine should considerably enhance the reaction rate. Indeed, this was achieved by the addition of cyclohexanone right from the beginning of the reaction. Figure 6 shows the

The influence of the Xantphos/Ru ratio was examined in catalytic experiments, monitoring conversion over time (Figure 5). A Xantphos/Ru ratio of 1/2 led to reduced activity, while

Figure 6. Reaction profile for the amination of cyclohexanol in the presence of additional cyclohexanone: (■) cyclohexanol; (●) cyclohexylamine; (▲) dicyclohexylimine; (▼) cyclohexylimine; (◆) cyclohexanone. Conditions: 1 mol % of RuHCl(CO)(PPh3)3, 1 mol % of Xantphos, 5 mmol of cyclohexanol, 0.5 mmol of cyclohexanone, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

reaction profile with 10 mol % of ketone added. Only a small portion of the added ketone was observed during the reaction, the major intermediates being the secondary and primary imines (k1 ≪ k2, Scheme 4). The reaction was finished within 12 h, in comparison to the reaction without added ketone, which took 30 h for completion (Figure 1). As the concentration of product primary amine increases during the reaction, also the equilibria leading to the formation of dicyclohexylimine will play an increasing role in the total rate. All assumptions and observations made above were confirmed for varying amounts of ketone added (see Figure S7 in the Supporting Information). Catalyst Deactivation and Activation. As it is assumed that the reaction proceeds via a Ru dihydride intermediate, RuH2(CO)(PPh3)3 was used as the precursor. In combination with Xantphos this complex was completely inactive in the direct amination of cyclohexanol under the standard conditions given in Figure 1 (Figure 7). This makes sense, as in the absence of any hydrogen acceptor the coordinatively saturated species cannot enter the catalytic cycle to dehydrogenate the alcohol. This would occur if no hydrogen was eliminated from the complex, which obviously does not take place. However, again, added ketone (imine) should be able to act as a hydrogen

Figure 5. Reaction profiles for the amination of cyclohexanol with varying Xantphos/Ru ratios: (●) 1/2; (▲) 1/1; (■) 2/1. Conditions: 1 mol % of RuHCl(CO)(PPh3)3, Xantphos, 5 mmol of cyclohexanol, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

approximately the same activity was observed for ratios of 1/1 and 2/1, suggesting coordination of one Xantphos ligand to ruthenium in the active species. Next, we addressed a dilemma intrinsically hampering all kind of reactions following the “borrowing hydrogen” methodology. As we are dealing with a sequence of consecutive reactions (Scheme 4) and coupled equilibria, none of the intermediates (ketone, imine) can be present in a higher concentration than the catalyst loading. That means no matter how high the intrinsic rate constants, reactions will be slow due to very low concentrations. Assuming now that. at the high excess of NH3 used and high temperature applied, the condensation of the ketone to form the imine is fast,14 both imine and RuH2 species are present only in low amounts (in the examples given above, the catalyst loading is 1 mol %). That 1625

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Figure 7. RuH2(CO)(PPh3)3/Xantphos activation using different ketones: (■) no ketone; (●) cyclohexanone; (▲) cyclooctanone; (▼) cyclopentanone. Conditions: 1 mol % of RuH2(CO)(PPh3)3, 1 mol % of Xantphos, 5 mmol of cyclohexanol, 10 mol % of ketone, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

Figure 8. Reaction profile for the amination of cyclohexanol, with addition of KOtBu: (●) 1 mol %; (▲) 4 mol %; (■) 10 mol %. Conditions: 1 mol % of RuHCl(CO)(PPh3)3, 1 mol % of Xantphos, 5 mmol of cyclohexanol, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

acceptor and activate the catalyst. Indeed, the addition of various ketones activated this precursor via the formed imine (Figure 7). In Scheme 5 a proposed mechanism is given for this step. It has to be noted that neither PPh3 nor CO necessarily remains Scheme 5. Activation of a Dihydride Precursor by Cyclohexylimine

Figure 9. Reaction profile for the amination of cyclohexanol, with addition of KOtBu and cyclohexanone: (■) cyclohexanol; (●) cyclohexylamine; (▲) dicyclohexylimine; (▼) cyclohexylimine; (◆) cyclohexanone. Conditions: 1 mol % of RuHCl(CO)(PPh3)3, 1 mol % of Xantphos, 5 mmol of cyclohexanol, 10 mol % of KOtBu, 10 mol % of cyclohexanone, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

coordinated during the process. The coordinatively unsaturated Ru species that is formed, most likely stabilized by other reaction components present, can then enter the catalytic cycle.10,15 In an attempt to promote the activation of the RuHCl(CO)(PPh3)3(Xantphos) precursor by HCl abstraction, a strong base (KOtBu) was added. Unexpectedly, the complex was now deactivated (Figure 8). However, even more remarkably, the reaction behaved “normally” again when a combination of both base and cyclohexanone was used (Figure 9). The addition of a strong base apparently leads to an inactive species that can possibly be activated by the imine, as was observed for the Ru dihydride precursor. Thus, the reaction was performed again in a NMR tube. Here RuHCl(CO)(PPh3)3/ Xantphos was dissolved in toluene-d8 and refluxed for 3 h. After this, KOtBu and cyclohexanol were added. The 1H NMR spectrum revealed the formation of a different species. On comparison of the resulting spectrum (Figure 10) to the Ru dihydride precursor in combination with Xantphos, these

Figure 10. (top) 1H NMR of the hydride region of RuHCl(CO)(PPh3)3/Xantphos with KOtBu and cyclohexanol after 12 h reflux and (bottom) 1H NMR of the hydride region of RuH2(CO)(PPh3)3/ Xantphos (complex 2), after 3 h reflux (d8-toluene, 400 MHz, 298 K): δ −6.69 (dddd, JHH = 6.6 Hz, JHP = 15, 28, 35 Hz), −8.75 (dddd, JHH = 6.6 Hz, JHP = 27, 34, 77 Hz).13

appear to be very similar. The complex RuH2(CO)(PPh3)(Xantphos), previously described by Williams,16 exhibits exactly the same coupling constants as the newly observed complex 1626

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Notable is a short distance of 2.3020(19) Å between the Ru atom and the oxygen of the xanthene backbone, indicating a coordination bond. The remaining PPh3 resides in an equatorial position with the Xantphos, leaving both chlorides at the axial positions (Figure 12), slightly offset from 180° angle with each other.

from the mixture of RuHCl(CO)(PPh3)3/Xantphos with KOtBu/cyclohexanol. Hence we conclude that RuHCl(CO)(PPh3)(Xantphos) is converted by KOtBu in the presence of cyclohexanol into RuH2(CO)(PPh3)(Xantphos). The remaining excess of KOtBu might lead to side reactions such as aldol condensation, leading to undesirable effects. Variation of Catalyst Precursors. We were interested whether other Ru(II) precursors, especially those without CO, can also give active catalysts. Under standard conditions, i.e. without any additive, RuCl2(PPh3)4 in combination with Xantphos gave no conversion (Figure 11). However, addition

Figure 12. Structure of RuCl2(PPh3)(Xantphos) (complex 3) in the crystal.19 Displacement ellipsoids are displayed at the 50% probability level. Only the major disorder component is shown. A partially occupied, disordered toluene solvent molecule was omitted for clarity. Selected bond lengths (Å) and angles (deg) with standard uncertainties in parentheses: Ru(1)−Cl(1) = 2.4114(8), Ru(1)− Cl(2) = 2.4070(8), Ru(1)−P(1) = 2.3335(8), Ru(1)−P(2) = 2.3418(8), Ru(1)−P(3) = 2.2487(8), Ru(1)−O(1) = 2.3020(19); P(1)−Ru(1)−P(2) = 159.21(3), P(1)−Ru(1)−P(3) = 99.83(3), P(2)−Ru(1)−P(3) = 99.63(3), P(3)−Ru(1)−O(1) = 179.45(6), Cl(1)−Ru(1)−Cl(2) = 169.20(3).

Figure 11. RuCl2(PPh3)4 activation by KOtBu in different amounts: (■) 0 mol %; (▼) 1 mol %; (●) 4 mol %, (▲) 10 mol %. Conditions: 1 mol % of RuCl2(PPh3)4, 1 mol % of Xantphos, 5 mmol of cyclohexanol, KOtBu, 15 mL of tert-amyl alcohol, 2.5 mL NH3(l) (97.5 mmol), 150 °C.

of KOtBu led to an active catalyst. It is expected that chloride abstraction generates a vacant site which can bind the alkoxide. β-Hydrogen abstraction will then lead to a hydrido chloro complex (Scheme 6),17 which in turn could be activated by

After addition of KOtBu to a solution of RuCl2(PPh3)4/ Xantphos and cyclohexanol in d8-toluene and refluxing for 12 h, a hydride signal had appeared in the 1H NMR spectrum at −16.5 ppm, split as a doublet of triplets. This is in agreement with a structure such as RuHCl(PPh3)(Xantphos) (4), which was previously reported and characterized by Williams.20 The doublet of triplets results from the hydride coupling with two equal phosphines and one different phosphine. As in the dichloro complex, also in the hydrido chloro complex, Xantphos is also coordinated via the oxygen atom in the backbone (Figure 12). The corresponding 31P NMR is shown in Figure S1 (Supporting Information). As RuCl2(PPh3)(Xantphos) is inactive but can be activated with KOtBu, it is expected that RuHCl(PPh3)3/Xantphos (4) will be active without an additive. As seen from Figure 13, this is indeed the case. The activity is only slightly lower than for RuHCl(CO)(PPh3)3/Xantphos (1) (Figure 1). The 1H NMR spectrum of the RuHCl(PPh3)3 precursor shows a quartet in the hydride region. After reflux in the presence of Xantphos the signal changes to a doublet of triplets. In addition, the 31P NMR changes to a mixture of two species, resembling the spectrum observed for RuCl2(PPh3)(Xantphos) after treatment with KOtBu.21 Mechanism. From the combined results obtained a mechanism can be proposed (Scheme 7) in agreement with all catalysis and NMR data. Starting from any hydrido chloro complex (with or without CO) in the presence of the alcohol, ammonia can abstract HCl to form NH4Cl and an alkoxide species. This can undergo β-hydrogen elimination, giving the

Scheme 6. Activation of a Ru Dichloride Precursor by KOtBu

NH3 in the same way as described earlier for RuHCl(CO)(PPh3)(Xantphos) (Scheme 3). It appears that 1 equiv of KOtBu is sufficient to give an active catalyst, while higher amounts of base lead to lower activity again, though the catalyst stays active up to 10 mol % of base (Figure 11). Similar observations were made for RuCl2(PPh3)3 as precursor (see the Supporting Information).18 The resulting mixture of the reaction of RuCl2(PPh3)4 with Xantphos (3) exhibits a doublet and a triplet in the 31P NMR spectrum, which indicates trans coordination of the two Xantphos P atoms with the remaining PPh3 in a cis position. Single crystals were grown from this mixture in d8-toluene at low temperature. The structure shows a distorted octahedron with the two phosphorus atoms of Xantphos in trans positions. 1627

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RuH2(CO)(PPh3)3/Xantphos requires activation by an imine (ketone in the presence of NH3 under reaction conditions).

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Scheme 7. Proposed Mechanism for the Amination of Alcohols using RuHCl(CO)(PPh3)3/Xantphos

CONCLUSIONS On combination of the data obtained in catalytic experiments and NMR investigations, a dihydrido Ru species was identified as an intermediate species in the direct amination of cyclohexanol with NH3. It was shown that hydrido chloro Ru precursor complexes can be activated by NH3 under reaction conditions in the presence of alcohol. This does not require the presence of a CO ligand in the starting complex. Dichloro Ru precursor complexes require a stronger base (KOtBu) for activation. We have pointed out that the “hydrogen shuttling” processes tend to be intrinsically hampered by a low steadystate concentration of intermediates. In the case of the direct amination of cyclohexanol, this has been overcome by the addition of the corresponding ketone, providing a higher concentration of imine from the start of the reaction. On the basis of the combined findings, a mechanism for the complete catalytic cycle was proposed.

ketone and a RuH2(L)n(Xantphos) species. The Ru dihydride species hydrogenates the imine and generates an active species, which enters the catalytic cycle. However, as the hydrogen shuttling is very closely related to transfer hydrogenation and the Meerwein−Ponndorf−Verley mechanism, it might be that after the initiation, a different mechanism is followed, more in line with the transfer hydrogenation mechanisms.22 Using dichloro Ru precursors such as RuCl2(PPh3)4/ Xantphos requires a (strong) base to form the hydrido chloro Ru species 4 in order to enter the catalytic cycle. On the other hand, starting from a Ru dihydride complex 2 such as

Procedures for the Amination of Cyclohexanol. With RuHCl(CO)(PPh3)3/Xantphos. RuHCl(CO)(PPh3)3 (0.05 mmol, 1 mol %, 47.6 mg) was weighed into a Schlenk tube and was purged with argon. To this was added dry degassed tert-amyl alcohol (15 mL). Subsequently, Xantphos (0.05 mmol, 1 mol %, 29 mg) and the cyclohexanol (5 mmol, 0.53 mL) were added. The solution was transferred to a homemade 75 mL stainless steel autoclave, which was purged with argon. The autoclave was charged with liquid ammonia (2.5 mL, 97.5 mmol) and then heated for the appropriate time. With RuHCl(CO)(PPh3)3/Xantphos and Additional Ketone. RuHCl(CO)(PPh3)3 (0.05 mmol, 1 mol %, 47.6 mg) was weighed into a Schlenk tube and was purged with argon. To this was added dry degassed tert-amyl alcohol (15 mL). Subsequently, Xantphos (0.05 mmol, 1 mol %, 29 mg) and the cyclohexanol were added (5 mmol, 0.53 mL). To the solution was added the appropriate amount of cyclohexanone (0.2−1.25 mmol, 2.5−25 mol %) with a micropipet. The solution was transferred to a homemade 75 mL stainless steel autoclave, which was purged with argon. The autoclave was charged with liquid ammonia (2.5 mL, 97.5 mmol) and then heated for the appropriate time. With RuHCl(CO)(PPh3)3/Xantphos) and KOtBu. RuHCl(CO)(PPh3)3 (0.05 mmol, 1 mol %, 47.6 mg) was weighed into a Schlenk tube and was purged with argon. To this was added dry degassed tertamyl alcohol (15 mL). Subsequently, Xantphos (0.05 mmol, 1 mol %, 29 mg) and cyclohexanol were added (5 mmol, 0.53 mL). The solution was transferred to a homemade 75 mL stainless steel autoclave, which was purged with argon. After this, KOtBu (1−10 mol %, 0.05−0.5 mmol; see Figure 7) was added to the mixture and the autoclave was charged with liquid ammonia (2.5 mL, 97.5 mmol) and then heated for the appropriate time. With RuH2(CO)(PPh3)3/Xantphos. RuH2(CO)(PPh3)3 (0.05 mmol, 1 mol %, 46 mg) was weighed into a Schlenk tube and was purged with argon. To this was added dry degassed tert-amyl alcohol (15 mL). Subsequently, Xantphos (0.05 mmol, 1 mol %, 29 mg) and the cyclohexanol were added (5 mmol, 0.53 mL). After this, ketone (0.5 mmol, 10 mol %; see Figure 6 for different ketones) was added. The solution was transferred to a homemade 75 mL stainless steel autoclave, which was purged with argon. The autoclave was charged with liquid ammonia (2.5 mL, 97.5 mmol) and then heated for the appropriate time. With RuCl2(PPh3)n (n = 3, 4)/Xantphos. RuCl2(PPh3)3 (0.05 mmol, 1 mol %, 47.9 mg) or RuCl2(PPh3)4 (0.05 mmol, 1 mol %, 61.1 mg) was weighed into a Schlenk tube and was purged with argon. To this was added dry degassed tert-amyl alcohol (15 mL). Subsequently, Xantphos (0.05 mmol, 1 mol %, 29 mg) and cyclohexanol were added

Figure 13. Reaction profile for the amination of cyclohexanol with RuHCl(PPh3)3/Xantphos (complex 4): (■) cyclohexanol; (●) cyclohexylamine; (▲) dicyclohexylimine; (▼) cyclohexanone, (◆) cyclohexylimine. Conditions: 1 mol % of RuHCl(PPh3)3, 1 mol % of Xantphos, 5 mmol of cyclohexanol, 15 mL of tert-amyl alcohol, 2.5 mL of NH3(l) (97.5 mmol), 150 °C.

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(5 mmol, 0.53 mL). After this, KOtBu (0−10 mol % 0−0.5 mmol; see Figure 9 for different amounts) was added. The solution was transferred to a homemade 75 mL stainless steel autoclave, which was purged with argon. The autoclave was charged with liquid ammonia (2.5 mL, 97.5 mmol) and then heated for the appropriate time. Procedures for the in Situ NMR Experiments. RuHCl(CO)(PPh3)3/Xantphos. RuHCl(CO)(PPh3)3 (0.04 mmol, 38.1 mg) was weighed into a Wilmad-Young NMR tube. Subsequently, Xantphos was added (0.04 mmol, 23.1 mg) and was purged with argon. To this was added dry degassed toluene-d8 (0.5 mL). The mixture was refluxed for 3 h in the closed tube. After cooling, both 1H and 31P NMR were recorded. After this, base (1 equiv, 0.04 mmol, 4.5 mg) and cyclohexanol (5 equiv, 0.2 mmol, 20 μL) were added and 1H and 31 P NMR spectra were recorded again. RuH2(CO)(PPh3)3/Xantphos. RuH2(CO)(PPh3)3 (0.04 mmol, 36.6 mg) was weighed into a Wilmad-Young NMR tube that was purged with argon. Subsequently, Xantphos was added (0.04 mmol, 23.1 mg). To this was added dry degassed toluene-d8 (0.5 mL). The mixture was refluxed for 3 h in the closed tube. After cooling, both 1H and 31P NMR were recorded. RuCl2(PPh3)4/Xantphos. RuCl2(PPh3)4 (0.04 mmol, 48.8 mg) was weighed into a Wilmad-Young NMR tube. Subsequently, Xantphos was added (0.04 mmol, 23.1 mg) and the tube was purged with argon. To this was added dry degassed toluene-d8 (0.5 mL). The mixture was refluxed for 3 h in the closed tube. After cooling, both 1H and 31P NMR were recorded. After this, base (1 equiv, 0.04 mmol, 4.5 mg) and cyclohexanol (5 equiv, 0.2 mmol, 20 μL) were added and 1H and 31P spectra were recorded again. Subsequently, KOtBu and cyclohexanol were added and the mixture was refluxed again for 12 h. After this time, the mixture was cooled and 1 H and 31P were recorded again. RuHCl(PPh3)3/Xantphos. RuHCl(PPh3)3 (0.04 mmol, 37 mg) was weighed into a Wilmad-Young NMR tube. Subsequently, Xantphos was added (0.04 mmol, 23.1 mg) and the tube was purged with argon. To this was added dry degassed toluene-d8 (0.5 mL). The mixture was refluxed for 3 h in the closed tube. After cooling, both 1H and 31P NMR were recorded.

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REFERENCES

(1) (a) Pingen, D.; Müller, C.; Vogt, D. Angew. Chem., Int. Ed. 2010, 49, 8130. (b) Pingen, D.; Diebolt, O.; Vogt, D. ChemCatChem 2013, 5, 2905−2912. (c) Pingen, D.; Vogt, D. Catal. Sci. Technol. 2014, 4, 47− 52. (2) (a) Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007, 349, 1555. (b) Lamb, G. W.; Williams, J. M. J. Chimica Oggi 2008, 26, 17. (c) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J. Dalton Trans. 2009, 753. (3) (a) Guillena, G.; Ramon, D. J.; Yus, M. Chem. Rev. 2010, 110, 1611. (b) Martinez-Asencio, A.; Ramon, D. J.; Yus, M. Tetrahedron 2011, 67, 3140−3149. (c) Martinez-Asencio, A.; Yus, M.; Ramon, D. J. Synthesis 2011, 2011, 3730−3740. (4) Watson, A. J. A.; Williams, J. M. J. Science 2010, 329, 635. (5) Gunanathan, C.; Milstein, D. Angew. Chem., Int. Ed. 2008, 47, 8661. (6) (a) Imm, S.; Bähn, S.; Neubert, L.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010, 49, 8126. (b) Imm, S.; Bähn, S.; Zhang, M.; Neubert, L.; Neumann, H.; Klasovsky, F.; Pfeffer, J.; Haas, T.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 7599. (7) Baumann, W.; Spannenberg, A.; Pfeffer, J.; Haas, T.; Köckritz, A.; Martin, A.; Deutsch, J. Chem. Eur. J. 2013, 19, 17702−17706. (8) RuHCl(CO)(PPh3)(Xantphos) crystallizes enantiomerically pure in the monoclinic space group P21 (No. 4): a = 15.0327(7) Å, b = 11.5362(3) Å, c = 16.0877(7) Å. β = 111.760(2)°, V = 2591.14(18) Å3. Further information is given in the Supporting Information. (9) Grushin, V. V. Acc. Chem. Res. 1993, 26, 279. (10) Wu, A.; Patrick, B. O.; Chung, E.; James, B. R. Dalton Trans. 2012, 41, 11093. (11) Chmely, S. C.; Kim, S.; Ciesielski, P. N; Jiménez-Osés, G.; Paton, R. S.; Beckham, G. T. ACS Catal. 2013, 3, 963. (12) Muthaiah, S.; Hong, S. H. Adv. Synth. Catal. 2012, 354, 3045− 3053. (13) See Figure S6 in the Supporting Information. (14) This is in agreement with the observed reaction profiles, where only primary and secondary imine was observed as intermediates in the GC. (15) Gunanathan, C.; Gnanaprakasam, B.; Iron, M. A.; Shimon, L. J. W.; Milstein, D. J. Am. Chem. Soc. 2010, 132, 14763. (16) Ledger, A. E. W.; Slatford, P. A.; Lowe, J. P.; Mahon, M. F.; Whittlesey, M. K.; Williams, J. M. J. Dalton Trans. 2009, 716. (17) Aranyos, A.; Csjernyik, G.; Szabó, K. J.; Bäckvall, J.-E. Chem. Commun. 1999, 351. (18) See Figure S8 in the Supporting Information. (19) RuCl2(PPh3)(Xantphos) crystallizes as a racemate in the triclinic space group P1̅ (No. 2): a = 11.3255(3) Å, b = 12.3579(5) Å, c = 20.3347(5) Å. α = 106.649(2)°, β=102.056(1)°, γ = 90.409(2)°, V = 2659.71(15) Å3. Further information is given in the Supporting Information. (20) Ledger, A. E. W.; Moreno, A.; Ellul, C. E.; Mahon, M. F.; Pregosin, P. S.; Whittlesey, M. K.; Williams, J. M. J. Inorg. Chem. 2010, 49, 7244. (21) For comparison see Figures 2 and 3 for RuCl2(PPh3) (Xantphos) after the reaction with KOtBu and cyclohexanol and Figures S4 and S5 for RuHCl(PPh3)(Xantphos) in the Supporting Information. (22) (a) Moulton, W. N.; Atta, R. E. V.; Ruch, R. R. J. Org. Chem. 1960, 26, 290. (b) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord. Chem. Rev. 2004, 248, 2201. (c) Hounjet, L. J.; Ferguson, M. J.; Cowie, M. Organometallics 2011, 30, 4108.

ASSOCIATED CONTENT

S Supporting Information *

Text, figures, and a table and CIF file giving experimental methods and crystallographic data and analysis methods. This material is available free of charge via the Internet at http:// pubs.acs.org.

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Article

AUTHOR INFORMATION

Corresponding Author

*E-mail for D.V.: [email protected]. Author Contributions

All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research has been funded by The Netherlands Ministry of Economic Affairs and The Netherlands Ministry of Education, Culture, and Sciences within the framework of the CatchBio program. The X-ray diffractometer was financed by The Netherlands Organization for Scientific Research (NWO). We thank Ton Staring for his technical assistance and Prof. Paul C. J. Kamer for valuable discussions. 1629

dx.doi.org/10.1021/om4011998 | Organometallics 2014, 33, 1623−1629