Wasserscheid P., Welton T. - Ionic Liquids in Synthesis (2002)(en)

226Peter Wasserscheid

5.2.3

Methods of Analysis of Transition Metal Catalysts in Ionic Liquids

Many transition metal-catalyzed reactions have already been studied in ionic liquids. In several cases, significant differences in activity and selectivity from their counterparts in conventional organic media have been observed (see Section 5.2.4). However, almost all attempts so far to explain the special reactivity of catalysts in ionic liquids have been based on product analysis. Even if it is correct to argue that a catalyst is more active because it produces more product, this is not the type of explanation that can help in the development of a more general understanding of what happens to a transition metal complex under catalytic conditions in a certain ionic liquid. Clearly, much more spectroscopic and analytical work is needed to provide better understanding of the nature of an active catalytic species in ionic liquids and to explain some of the observed “ionic liquid” effects on a rational, molecular level.

In general, most of the methods used to analyze the chemical nature of the ionic liquid itself, as described in Chapter 4, should also be applicable, in some more sophisticated form, to study the nature of a catalyst dissolved in the ionic liquid. For attempts to apply spectroscopic methods to the analysis of active catalysts in ionic liquids, however, it is important to consider three aspects: a) as with catalysis in conventional media, the lifetime of the catalytically active species will be very short, making it difficult to observe, b) in a realistic catalytic scenario the concentration of the catalyst in the ionic liquid will be very low, and c) the presence and concentration of the substrate will influence the catalyst/ionic liquid interaction. These three concerns alone clearly show that an ionic liquid/substrate/catalyst system is quite complex and may be not easy to study by spectroscopic methods.

One obvious approach involves the application of in situ NMR spectroscopy.

However, this method often suffers from the relatively low concentration of the catalyst in the ionic liquid. Moreover, 1H and 13C NMR spectroscopic investigations are difficult, since the intense signals of the ionic liquid make clear detection of the dissolved catalyst difficult. Several approaches to overcome the latter problem have been suggested. Hardacre and co-workers have described the synthesis and application of fully deuterated ionic liquids [39]. Alternatively, deuterium can be selec-

tively introduced into the ligand of the transition metal catalyst in order to study the complex dissolved in the ionic liquid by in situ 2H NMR spectroscopy [40]. The lat-

ter method has been used to investigate the activation of the square-planar Ni-com- plex (η-4-cycloocten-1-yl](1,5-diphenyl-2,4-pentanedionato-O,O´)nickel in slightly acidic chloroaluminate ionic liquids. The deuterated analogue of this complex was prepared according to Scheme 5.2-6, by treatment of 1,5-diphenyl-2,4-pentanedione

with NaH, followed by hydrolysis with D2O. The deuterated ligand was dried and treated with dicyclooctadienyl nickel Ni(COD)2.

2HNMR spectra of the deuterated complex obtained in CH2Cl2 and in [EMIM]Cl/AlCl3 (1:1.2) are displayed in Figure 5.2-3.

While the deuterated complex shows the expected NMR signals in CH2Cl2 (two signals from the complex and one signal from the solvent), the 2H NMR spectrum

			5.2 Transition Metal Catalysis in Ionic Liquids 227
			H(D)
			H	O
	O	H
			Ni	D(H)
		H
	O			O

+ NaH	-H2	+ Ni(COD)2

	-
O	+ D2O	O	H
Na+	H	O	D
O

Scheme 5.2-6: Synthesis of a deuterated analogue of the square-planar Ni-complex (η-4- cycloocten-1-yl](1,5-diphenyl-2,4-pentanedionato-O,O’)nickel for 2H NMR investigations.

obtained from the complex in the slightly acidic chloroaluminate ionic liquid shows only one signal, indicating that the abstraction of COD is more efficient in the ionic liquid medium. Moreover, the deuterium signal of the acac ligand undergoes a significant downfield shift, suggesting intense electronic interaction between the ligand and the Lewis acidic centers of the melt. These interactions, which should result in an increased electrophilicity of the Ni-center, help to explain the activation of Ni-acac complexes in slightly acidic chloroaluminate ionic liquids.

This example should illustrate that in situ NMR spectroscopy can be a powerful tool with which to study catalysts dissolved in ionic liquids, if the signals of the metal complex can be detected in sufficient intensity independently from the signals of the ionic liquid.

If this is not possible for any reason, an alternative way to obtain some insight into interactions between the catalyst complex and the ionic liquid may be to record changes in the ionic liquid during the catalytic process in an indirect manner. This method has been successfully used by the author’s group to understand the activation of (PPh3)2PtCl2 in chlorostannate ionic liquids in more detail. The change in color from yellow to red during the dissolution of the complex in the ionic liquid was attributed to the abstraction of chloride from the Pt-complex by the acidic [Sn2Cl5]– species of the ionic liquid. It proved possible to support this assumption by recording the Lewis acidity of the chlorostannate ionic liquid by 119Sn NMR before and after the addition of (PPh3)2PtCl2 [28]. The results of this investigation corresponded very well to an acid–base reaction of both chloride atoms of the platinum complex with the acidic ionic liquid.

228 Peter Wasserscheid

Figure 5.2-3: 2H NMR spectra of the deuterated analogue of the square planar Ni-complex (η-4-cycloocten-1-yl](1,5-diphenyl-2,4-pentanedionato-O,O’)nickel recorded [EMIM]Cl/AlCl3 [X(AlCl3) = 0.55] and in CH2Cl2.

In addition to in situ NMR spectroscopy, other methods such as in situ IR spectroscopy, EXAFS, and electrochemistry should be very useful for the investigation of active catalytic species in ionic liquids. However, far too little effort has been directed to this end in recent years.

This is surprising in view of the fact that a great deal of effort was made to study transition metal complexes in chloroaluminate ionic liquids in the 1980s and early 1990s (see Section 6.1 for some examples). The investigations at this time generally started with electrochemical studies [41], but also included spectroscopic and complex chemistry experiments [42].

5.2 Transition Metal Catalysis in Ionic Liquids 229

Obviously, with the development of the first catalytic reactions in ionic liquids, the general research focus turned away from basic studies of metal complexes dissolved in ionic liquids. Today there is a clear lack of fundamental understanding of many catalytic processes in ionic liquids on a molecular level. Much more fundamental work is undoubtedly needed and should be encouraged in order to speed up the future development of transition metal catalysis in ionic liquids.

5.2.4

Selected Examples of the Application of Ionic Liquids in Transition Metal Catalysis

5.2.4.1Hydrogenation

In general, transition metal-catalyzed hydrogenation reactions in ionic liquids are particularly promising. On the one hand, a large number of known, ionic hydrogenation catalysts are available [43]. On the other, the solubility of many alkenes and the availability of hydrogen in many ionic liquids appear to be sufficiently high for good reaction rates to be achieved. In this context it is noteworthy that the availability of hydrogen results not only from its solubility under equilibrium conditions, but also reflects the ease of its transfer from the gas phase into the melt. Since the diffusion of hydrogen into ionic liquids has been found to be relatively fast, the latter contribution is of special importance [44]. Finally, the miscibility gap between the saturated reaction products and the ionic liquid is often large, so that a biphasic procedure is possible in the majority of cases.

The first successful hydrogenation reactions in ionic liquids were studied by the groups of de Souza [45] and Chauvin [46] in 1995. De Souza et al. investigated the Rh-catalyzed hydrogenation of cyclohexene in 1-n-butyl-3-methylimidazolium ([BMIM]) tetrafluoroborate. Chauvin et al. dissolved the cationic “Osborn complex” [Rh(nbd)(PPh3)2][PF6] (nbd = norbornadiene) in ionic liquids with weakly coordinating anions (e.g., [PF6]–, [BF4]–, and [SbF6]–) and used the obtained ionic catalyst solutions for the biphasic hydrogenation of 1-pentene as seen in Scheme 5.2-7.

Although the reactants have only limited solubility in the catalyst phase, the rates of hydrogenation in [BMIM][SbF6] are almost five times faster than for the comparable reaction in acetone. All ionic catalyst solutions tested could be reused repeatedly. The loss of rhodium through leaching into the organic phase lay below the detection limit of 0.02 %. These results are of general importance for the field of

+ H2, [Rh(nbd)(PPh3)2]

in N + N

[A]-

C4H9

[A]-= [BF4]-, [PF6]-, [SbF6]-

Scheme 5.2-7: Biphasic hydrogenation of 1-pentene with the cationic “Osborn complex” [Rh(nbd)(PPh3)2][PF6] (nbd = norbornadiene) in ionic liquids with weakly coordinating anions.

230 Peter Wasserscheid

biphasic catalysis, since this was the first time that a rhodium catalyst was able to be “immobilized” in a polar solution without the use of specially designed ligands.

Chauvin’s group described the selective hydrogenation of cyclohexadiene to cyclohexene through making use of the biphasic reaction system [46]. Since the solubility of cyclohexadiene in [BMIM][SbF6] is about five times higher than the solubility of cyclohexene in the same ionic liquid, the latter was obtained in 98 % selectivity at 96 % conversion.

Rhodiumand cobalt-catalyzed hydrogenation of butadiene and 1-hexene [47, 48] and the Ru-catalyzed hydrogenation of aromatic compounds [49] and acryloni- trile–butadiene copolymers [50] have also been reported to be successful in ionic liquids.

An example of a stereoselective hydrogenation in ionic liquids was recently successfully demonstrated by Drießen-Hölscher et al. On the basis of investigations into the biphasic water/n-heptane system [51], the ruthenium-catalyzed hydrogenation of sorbic acid to cis-3-hexenoic acid in the [BMIM][PF6]/MTBE system was studied [52], as shown in Scheme 5.2-8.

In comparison with polar organic solvents (such as glycol) a more than threefold increase in activity with comparable selectivity for cis-3-hexenoic acid was observed in the ionic liquid. This is explained by partial deactivation (through complexation) of the active catalytic center in those polar organic solvents that are able to dissolve the cationic Ru catalyst. In contrast, the ionic liquid [BMIM][PF6] is known to combine high solvation power for ionic metal complexes with relatively weak coordination strength. In this way, the catalyst can be dissolved in a “more innocent” environment than is the case if polar organic solvents are used. After the biphasic hydrogenation of sorbic acid, the ionic catalyst solution could be recovered by phase separation and reused repeatedly. Other examples of selective hydrogenation of dienes by use of cobalt [47] and palladium [53] catalysts have been reported by Dupont and de Souza.

A number of enantioselective hydrogenation reactions in ionic liquids have also been described. In all cases reported so far, the role of the ionic liquid was mainly to open up a new, facile way to recycle the expensive chiral metal complex used as the hydrogenation catalyst.

Chauvin et al. hydrogenated α-acetamidocinnamic acid to (S)-phenylalanine in the presence of a [Rh(cod)(–)-(diop)][PF6] catalyst in a [BMIM][SbF6] melt with 64 % ee [46].

O

+ H2, [Ru]

- Cat.

O

OH

OH

[PF ]- / MTBE

in

S(cis-3-hexenoic acid) = 85%

N

+ N

6

C4H9

Scheme 5.2-8: Stereoselective hydrogenation of sorbic acid in the [BMIM][PF6]/MTBE biphasic system.

5.2 Transition Metal Catalysis in Ionic Liquids 231

+ H2, Rh-BINAP

CO2H CO2H

in N + N	[BF ]-/ 2-propanol
	4
	C4H9

ee = 80%

Scheme 5.2-9: Hydrogenation of 2-phenylacrylic acid to (S)-2-phenylpropionic acid with the chiral complex [RuCl2(S)-BINAP]2NEt3 as catalyst in [BMIM][BF4].

Dupont et al. were able to obtain up to 80 % ee in the conversion of 2-phenyl- acrylic acid into (S)-2-phenylpropionic acid with the chiral [RuCl2(S)-BINAP]2NEt3 complex as catalyst in [BMIM][BF4] melts (Scheme 5.2-9) [54].

Both reactions were carried out under two-phase conditions with the help of an additional organic solvent (such as iPrOH). The catalyst could be reused with the same activity and enantioselectivity after decantation of the hydrogenation products. A more recent example, again by de Souza and Dupont, has been reported. They made a detailed study of the asymmetric hydrogenation of α-acetamidocin- namic acid and the kinetic resolution of methyl (±)-3-hydroxy-2-methylenebu- tanoate with chiral Rh(I) and Ru(II) complexes in [BMIM][BF4] and [BMIM][PF6] [55]. The authors described the remarkable effects of the molecular hydrogen concentration in the ionic catalyst layer on the conversion and enantioselectivity of these reactions. The solubility of hydrogen in [BMIM][BF4] was found to be almost four times higher than in [BMIM][PF6].

Hydrogenation reactions were among the first transformations to be successfully carried out in reaction systems consisting of an ionic liquid and compressed CO2 [56, 57]. While the conceptual aspects of this innovative, biphasic reaction mode are covered in more detail in Section 5.4, the specific applications reported by Tumas et al. [56] and Jessop et al. [57] once more demonstrate the great potential of transition metal-catalyzed hydrogenation in ionic liquids. Tumas and co-workers investigated the hydrogenation of olefins in the biphasic system [BMIM][PF6]/scCO2. After reaction, the ionic catalyst layer could be separated by simple decantation and could be reused up to four times [56].

Jessop and co-workers studied asymmetric hydrogenation reactions with the catalyst complex Ru(OAc)2(tolBINAP) dissolved in [BMIM][PF6]. In both reactions under investigation – the hydrogenation of tiglic acid (Scheme 5.2.10) and the hydrogenation of the precursor of the anti-inflammatory drug ibuprofen (Scheme 5.2.11) – no CO2 was present during the catalytic transformation. However, scCO2 was used in both cases to extract the reaction products from the reaction mixture when the reaction was complete.

Finally, a special example of transition metal-catalyzed hydrogenation in which the ionic liquid used does not provide a permanent biphasic reaction system should be mentioned. The hydrogenation of 2-butyne-1,4-diol, reported by Dyson et al., made use of an ionic liquid/water system that underwent a reversible two-

232 Peter Wasserscheid

			OH		Ru(OAc)2(R)-tolBINAP	OH
				+ H2
					[BMIM][PF6] / H2O
O					25 °C, 5 bar	O
					followed by extraction
					with scCO2	100% conversion
						99% ee

Scheme 5.2-10: Ru-catalyzed asymmetric hydrogenation of tiglic acid, followed by product extraction with scCO2.

	OH		Ru(OAc)2-tolBINAP	OH
		+ H2
O				O
			[BMIM][PF6] / MeOH

25°C, 100bar

followed by extraction (S)-ibuprofen with scCO2

85% ee

Scheme 5.2-11: Ru-catalyzed asymmetric hydrogenation of isobutylatropic acid, followed by extraction of the product ibuprofen with scCO2.

phase/single-phase transformation upon a temperature switch [58]. At room temperature, the ionic liquid 1-methyl-3-n-octyl imidazolium ([OMIM]) tetrafluoroborate containing the cationic Rh catalyst formed a separate layer with water containing the substrate. At 80 °C however, a homogeneous single-phase reaction could be carried out.

Temperature-dependent phase behavior was first applied to separate products from an ionic liquid/catalyst solution by de Souza and Dupont in the telomerization of butadiene and water [34]. This concept is especially attractive if one of the substrates shows limited solubility in the ionic liquid solvent.

5.2.4.2 Oxidation reactions

Catalytic oxidation reactions in ionic liquids have been investigated only very recently. This is somewhat surprising in view of the well known oxidation stability of ionic liquids, from electrochemical studies [11], and the great commercial importance of oxidation reactions. Moreover, for oxidation reactions with oxygen, the nonvolatile nature of the ionic liquid is of real advantage for the safety of the reaction. While the application of volatile organic solvents may be restricted by the formation of explosive mixtures in the gas phase, this problem does not arise if a nonvolatile ionic liquid is used as the solvent.

Howarth oxidized various aromatic aldehydes to the corresponding carboxylic acids with Ni(acac)2 dissolved in [BMIM][PF6] as the catalyst and oxygen at atmospheric pressure as the oxidant [59]. However, this reaction cannot be considered a

5.2 Transition Metal Catalysis in Ionic Liquids 233

real challenge. Moreover, the catalyst loading used for the described reaction was rather high (3 mol%).

Ley et al. reported oxidation of alcohols catalyzed by an ammonium perruthenate catalyst dissolved in [NEt4]Br and [EMIM][PF6] [60]. Oxygen or N-methylmorpholine N-oxide is used as the oxidant and the authors describe easy product recovery by solvent extraction and mention the possibility of reusing the ionic catalyst solution.

The oxidation of alkenes and allylic alcohols with the urea-H2O2 adduct (UHP) as oxidant and methyltrioxorhenium (MTO) dissolved in [EMIM][BF4] as catalyst was described by Abu-Omar et al. [61]. Both MTO and UHP dissolved completely in the ionic liquid. Conversions were found to depend on the reactivity of the olefin and the solubility of the olefinic substrate in the reactive layer. In general, the reaction rates of the epoxidation reaction were found to be comparable to those obtained in classical solvents.

Song and Roh investigated the epoxidation of compounds such as 2,2- dimethylchromene with a chiral MnIII(salen) complex (Jacobsen catalyst) in a mixture of [BMIM][PF6] and CH2Cl2 (1:4 v/v), using NaOCl as the oxidant (Scheme 5.2-12) [62].

The authors describe a clear enhancement of the catalyst activity by the addition of the ionic liquid even if the reaction medium consisted mainly of CH2Cl2. In the presence of the ionic liquid, 86 % conversion of 2,2-dimethylchromene was observed after 2 h. Without the ionic liquid the same conversion was obtained only after 6 h. In both cases the enantiomeric excess was as high as 96 %. Moreover, the ionic catalyst solution could be reused several times after product extraction, although the conversion dropped from 83 % to 53 % after five recycles; this was explained, according to the authors, by a slow degradation process of the MnIII complex.

A very exciting way to combine electrochemistry and transition metal catalysis in ionic liquids was reported by Gaillon and Bedioui [63], who investigated the electroassisted activation of molecular oxygen by Jacobsen’s epoxidation catalysts dissolved in [BMIM][PF6] and were able to provide evidence for the formation of the highly reactive oxomanganese(V) intermediate, which was not detectable in organic solvents. This may open new perspectives for clean, electroassisted oxidation reactions with molecular oxygen in ionic liquids.

O			chiral MnIII(salen)-catalyst				O
			(Jacobsen-catalyst), NaOCl
			in [BMIM][PF6] / CH2Cl2 (v/v=1/4)
			0°C, 2h					O
					yield= 86%
					ee= 96%

Scheme 5.2-12: Mn-catalyzed asymmetric epoxidation in a [BMIM][PF6]/CH2Cl2 (v/v = 1/4) solvent mixture.

234 Peter Wasserscheid

Finally, it should be mentioned that ionic liquids have successfully been used in classical, stoichiometric oxidation reactions as well. Singer et al., for example, described the application of [BMIM][BF4] in the oxidation of codeine methyl ether to thebaine [64]. The ionic liquid was used here as a very convenient solvent to extract excess MnO2 and associated impurities from the reaction mixture.

5.2.4.3 Hydroformylation

In hydroformylation, biphasic catalysis is a well established method for effective catalyst separation and recycling. In the case of Rh-catalyzed hydroformylation reactions, this principle is implemented technically in the Ruhrchemie–Rhône–Poulenc process, in which water is used as the catalyst phase [65]. Unfortunately, this process is limited to C2-C5-olefins, due to the low water solubility of higher olefins. Nevertheless, the hydroformylation of many higher olefins is of commercial interest. One example is the hydroformylation of 1-octene for the selective synthesis of linear nonanal. This can be obtained highly selectively by application of special ligand systems around the catalytic center. However, the additional costs associated with the use of these ligands make it even more economically attractive to develop new methods for efficient catalyst separation and recycling. In this context, biphasic catalysis with an ionic liquid as catalyst layer is a highly promising approach.

As early as 1972 Parshall described the platinum-catalyzed hydroformylation of ethene in tetraethylammonium trichlorostannate melts [1]. [NEt4][SnCl3], the ionic liquid used for these investigations, has a melting point of 78 °C. Recently, plat- inum-catalyzed hydroformylation in the room-temperature chlorostannate ionic liquid [BMIM]Cl/SnCl2 was studied in the author’s group. The hydroformylation of 1-octene was carried out with remarkable n/iso selectivities (Scheme 5.2-13) [66].

Despite the limited solubility of 1-octene in the ionic catalyst phase, a remarkable activity of the platinum catalyst was achieved [turnover frequency (TOF) = 126 h–1]. However, the system has to be carefully optimized to avoid significant formation of hydrogenated by-product. Detailed studies to identify the best reaction conditions revealed that, in the chlorostannate ionic liquid [BMIM]Cl/SnCl2 [X(SnCl2) = 0.55],

H

+ CO/H2, PtCl2(PPh3)2

n-product

O

+

O

in

N

+ N

C4H9

Cl- /SnCl2

H

[x(SnCl2)=0.51]

iso-product

120 °C, 90 bar CO/H2

n/iso: 19

Scheme 5.2-13: Biphasic, Pt-catalyzed hydroformylation of 1-octene with a slightly acidic [BMIM]Cl/SnCl2 ionic liquid as catalyst layer.

5.2 Transition Metal Catalysis in Ionic Liquids 235

the highest ratio of hydroformylation to hydrogenation was found at high syn-gas pressure and low temperature. At 80 °C and 90 bar CO/H2-pressure, more than 90 % of all products were n-nonanal and iso-nonanal, the ratio between these two hydroformylation products being as high as 98.6:1.4 (n/iso = 72.4) [66].

Moreover, these experiments reveal some unique properties of the chlorostannate ionic liquids. In contrast to other known ionic liquids, the chlorostannate system combine a certain Lewis acidity with high compatibility to functional groups. The first resulted, in the hydroformylation of 1-octene, in the activation of (PPh3)2PtCl2 by a Lewis acid–base reaction with the acidic ionic liquid medium. The high compatibility to functional groups was demonstrated by the catalytic reaction in the presence of CO and hydroformylation products.

Rutheniumand cobalt-catalyzed hydroformylation of internal and terminal alkenes in molten [PBu4]Br was reported by Knifton as early as in 1987 [2]. The author described a stabilization of the active ruthenium-carbonyl complex by the ionic medium. An increased catalyst lifetime at low synthesis gas pressures and higher temperatures was observed.

The first investigations of rhodium-catalyzed hydroformylation in room-temper- ature liquid molten salts were published by Chauvin et al. in 1995 [6, 67]. The hydroformylation of 1-pentene with the neutral Rh(CO)2(acac)/triarylphosphine catalyst system was carried out as a biphasic reaction with [BMIM][PF6] as the ionic liquid. With none of the ligands tested, however, was it possible to combine high activity, complete retention of the catalyst in the ionic liquid, and high selectivity for the desired linear hydroformylation product at that time. The use of PPh3 resulted in significant leaching of the Rh-catalyst out of the ionic liquid layer. In this case, the catalyst is active in both phases, which makes a clear interpretation of solvent effects on the reactivity difficult. The catalyst leaching could be suppressed by the application of sulfonated triaryl phosphine ligands, but a major decrease in catalytic activity was found with these ligands (TOF = 59 h–1 with tppms, compared to 333 h–1 with PPh3). Moreover, all of the ligands used in Chauvin’s work showed poor selectivity to the desired linear hydroformylation product (n/iso ratio between 2 and 4). Obviously, the Rh-catalyzed, biphasic hydroformylation of higher olefins in ionic liquids requires the use of ligand systems specifically designed for this application. These early results thus stimulated research into other immobilizing, ionic ligand systems that would provide good catalyst immobilization without deactivation of the catalyst.

A pioneering ligand system specially designed for use in ionic liquids was described in 2000 by Salzer et al. [68]. Cationic ligands with a cobaltocenium backbone were successfully used in the biphasic, Rh-catalyzed hydroformylation of 1-octene. 1,1’-Bis(diphenylphosphino) cobaltocenium hexafluorophosphate (cdpp) proved to be an especially promising ligand. The compound can be synthesized as shown in Scheme 5.2-14, by mild oxidation of 1,1’-bis(diphenylphosphino)co- baltocene with C2Cl6 and anion-exchange with [NH4][PF6] in acetone (for detailed ligand synthesis see [68]).

The results obtained in the biphasic hydroformylation of 1-octene are presented in Table 5.2-1. In order to evaluate the properties of the ionic diphosphine ligand