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Synopsis. A (NHC)Pd(cinnamyl)Cl complex with an enlarged N-heterocyclic carbene ligand is efficiently retained by a solvent-resistant nanofiltration m...
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Organometallics 2009, 28, 3922–3927 DOI: 10.1021/om900214j

Solvent-Resistant Nanofiltration of Enlarged (NHC)Pd(allyl)Cl Complexes for Cross-Coupling Reactions Dirk Schoeps,† Volodymyr Sashuk,† Katrin Ebert,§ and Herbert Plenio*,† †

Anorganische Chemie im Zintl-Institut, Technische Universit€ at Darmstadt, Petersenstrasse 18, 64287 Darmstadt, Germany, and §GKSS-Forschungszentrum Geesthacht GmbH, Institut f€ ur Polymerforschung, Max-Planck-Strasse 1, 21502 Geesthacht, Germany Received March 20, 2009

An enlarged imidazolinium salt with a molecular mass of nearly 800 g/mol was synthesized and the respective N-heterocyclic carbene (NHC= N,N0 -bis(2,6-diisopropyl-4-CH2NCy2-phenyl)-4,5-dihydroimidazol-2-ylidene) converted into (NHC)Pd(allyl)Cl and (NHC)Pd(cinnamyl)Cl complexes. The cinnamyl complex displays excellent activities in the Suzuki-Miyaura coupling and the BuchwaldHartwig amination. The separation of this complex from the coupling products by means of a solventresistant nanofiltration using a PDMS (polydimethylsiloxane) membrane on PAN (polyacrylonitrile) was tested, and very high retention of between 97% and 99.9% of the (NHC)Pd complex was observed. The residual Pd content in the cross-coupling products is in the range 3.5-25 ppm.

The separation of transition metal-based homogeneous catalyst complexes from the products of chemical reactions is important.1 First of all there is the chance to recover and reuse an expensive catalyst complex that is often composed of a valuable platinum group metal and an equally costly designer ligand.2 Second, most of the metals used for catalytic transformations have to be considered as toxic, and consequently tight limits for the contamination of chemical products apply, which can be met by catalyst removal.3 Thus it is not surprising that numerous approaches, such as the tagging of catalyst complexes with static4-7 or switchable phase tags,8,9 the use of soluble10-14 and insoluble supported catalysts,15-17 self-supported catalysts,18 nonco-

valent immobilization of catalysts,19 polymer-gel catalysts,20 microencapsulated catalysts,21 aqueous-organic phase catalyzed reactions,22-29 or the use of unusual solvent systems,30-32 were applied.33 A recent Chemical Reviews issue on facilitated synthesis summarizes many of these concepts.34 Another approach for catalyst separation is solventresistant nanofiltration.35 Following the catalytic transformation, the organic solvent holding both the product and the catalyst complex is filtered over a polymeric or (less often applied) a ceramic membrane. In a first approximation the molecular weight differences of the constituents govern the separation process in nanofiltration.36,37 Another important criterion deciding on the usefulness of the nanofiltration process is the flux of the solvent through the

*Corresponding author. E-mail: [email protected]. (1) Cole-Hamilton, D. J. Science 2003, 299, 1702. (2) Garrett, C. E.; Prasad, K. Adv. Synth. Catal. 2004, 346, 889. (3) European Medicines Agency, Guideline on the Specification Limits for Residues of Metal Catalysts, January 2007. (4) Yoshida, J.-I.; Itami, K. Chem. Rev. 2002, 102, 3693. (5) Rix, D.; Caijo, F.; Laurent, I.; Gulajski, L.; Grela, K.; Mauduit, M. Chem. Commun. 2007, 3771. (6) Remmele, H.; K€ ollhofer, A.; Plenio, H. Organometallics 2003, 22, 4098. (7) Yao, Q.; Sheets, M. J. Organomet. Chem. 2005, 690, 3577. (8) S€ ussner, M.; Plenio, H. Angew. Chem., Int. Ed. 2005, 44, 6885. (9) Desset, S. L.; Cole-Hamilton, D. J. Angew. Chem., Int. Ed. 2009, 48, 1472. (10) Bergbreiter, D. E.; Tian, J.; Hongfa, C. Chem. Rev. 2009, 109, 530. (11) an der Heiden, M. R.; Plenio, H. Chem.;Eur. J. 2004, 10, 1789. (12) Hillerich, J.; Plenio, H. Chem. Commun. 2003, 3024. (13) Datta, A.; Plenio, H. Chem. Commun. 2003, 1504. (14) Hongfa, C.; Su, H.-L.; Bazzi, H. S.; Bergbreiter, D. E. Org. Lett. 2009, 11, 665. (15) Buchmeiser, M. R. Chem. Rev. 2009, 109, 303. (16) Lu, J.; Toy, P. H. Chem. Rev. 2009, 109, 815. (17) Minakata, S.; Komatsu, M. Chem. Rev. 2009, 109, 711. (18) Wang, Z.; Chen, G.; Ding, K. Chem. Rev. 2009, 109, 322. (19) Fraile, J. M.; Garcia, J. I.; Mayoral, J. A. Chem. Rev. 2009, 109, 360.

(20) Ikegami, S.; Hamamoto, H. Chem. Rev. 2009, 109, 583. (21) Akiyama, R.; Kobayashi, S. Chem. Rev. 2009, 109, 594. (22) Shaughnessy, K. H. Chem. Rev. 2009, 109, 643. (23) Fleckenstein, C. A.; Plenio, H. Chem.;Eur. J. 2008, 14, 4267. (24) Fleckenstein, C. A.; Plenio, H. Green Chem. 2008, 10, 563. (25) Fleckenstein, C. A.; Plenio, H. J. Org. Chem. 2008, 73, 3236. (26) Fleckenstein, C. A.; Plenio, H. Chem.;Eur. J. 2007, 13, 2701. (27) Fleckenstein, C. A.; Plenio, H. Green Chem. 2007, 9, 1287. (28) Fleckenstein, C. A.; Roy, S.; Leuth€ausser, S.; Plenio, H. Chem. Commun. 2007, 2870. (29) Pschierer, J.; Plenio, H. Org. Lett. 2009, 11, 2551. (30) Solinas, M.; Jiang, J.; Stelzer, O.; Leitner, W. Angew. Chem., Int. Ed. 2005, 44, 2291. (31) Scurto, A. M.; Leitner, W. Chem. Commun. 2006, 3681. (32) da Costa, R. C.; Gladysz, J. A. Adv. Synth. Catal. 2007, 349 243. (33) Multiphase Homogeneous Catalysis; Cornils, B., Herrmann, W. A., Horvath, I. T., Leitner, W., Mecking, S., Olivier-Bourbigou, H., Vogt, D., Eds.; Wiley-VCH: Weinheim, 2005. (34) Bergbreiter, D. E.; Kobayashi, S. Chem. Rev. 2009, 109, 257. (35) Vandezande, P.; Gevers, L. E. M.; Vankelecom, I. F. J. Chem. Soc. Rev. 2008, 37, 365. (36) Koops, G. H.; Yamadaa, S.; Nakao, S.-I. J. Membr. Sci. 2001, 189, 241. (37) Scarpello, J. T.; Nair, D.; Santos, L. M. F. d.; White, L. S.; Livingston, A. G. J. Membr. Sci. 2002, 203, 71.

Introduction

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Organometallics, Vol. 28, No. 13, 2009

membrane.38 The incorporation of solvent into the polymeric membrane results in swelling and modulation of the membrane permeability and separation properties. Ideally, the efficient separation of large and small molecules is combined with a high solvent flux. Solvent-resistant nanofiltration has been applied for the separation of homogeneous catalysts.35,39-41 One approach is the use of dendrimers42,43 or polymers (such as linear polystyrene) in order to obtain enlarged catalysts with increased molecular weight, which are characterized by excellent retention properties.44 However, the high local concentration of active species on the surface of a dendrimer can lead to bimolecular deactivation (proximity effect) and thus a significant decrease in catalytic activity.45 With linear polymers the small content of active metal in the (pre) catalyst complex proves to be a drawback. Several groups have also reported on the nanofiltration of unmodified catalyst complexes, but the retention of the active species tends to be lower.46,47 We recently reported on the synthesis of enlarged Nheterocyclic carbenes and their application in the highly efficient solvent-resistant nanofiltration of Grubbs-Hoveydatype olefin metathesis catalysts.48 The present study focuses on the synthesis of new mass-tagged N-heterocyclic carbenes and the respective Nolan-type (NHC)Pd(allyl)Cl complexes.49,50 This approach is aimed toward combining the established excellent catalytic activity of such complexes in Suzuki and Buchwald-Hartwig amination reactions with the retention properties of enlarged complexes in solventresistant nanofiltration.

Results and Discussion Synthesis of (NHC)Pd(allyl)Cl Complexes. Mass-tagged NHC ligands with isopropyl groups in the ortho positions were synthesized using the (-CH2Cl)-substituted imidazolinium salt (1) recently reported by us.51 Nucleophilic substitution reactions at the -CH2Cl groups allow the facile introduction of various nucleophiles. The reaction of 1 with Cy2NH under Finkelstein conditions (i.e., in the presence of NaI) led to the synthesis of the imidazolium salt 2 in 93% yield bearing four cyclohexyl groups as mass tags (Scheme 1). (38) Vankelecom, I. F. J.; Smeta, K. D.; Gevers, L. E. M.; Livingston, A.; Nair, D.; Aerts, S.; Kuypers, S.; Jacobs, P. A. J. Membr. Sci. 2004, 231, 99. (39) Dijkstra, H. P.; van Klink, G. P. M.; van Koten, G. Acc. Chem. Res. 2002, 35, 798. (40) M€ uller, C.; Nijkamp, M. G.; Vogt, D. Eur. J. Inorg. Chem. 2005, 4011. (41) Gaikwad, A. V.; Boffa, V.; tenElshof, J. E.; Rothenberg, G. Angew. Chem., Int. Ed. 2008, 47, 5407. (42) Dijkstra, H. P.; Ronde, N.; Klink, G. P. M. v.; Vogt, D.; Koten, G. v. Adv. Synth. Catal. 2003, 345, 364. (43) Brinkmann, N.; Giebel, D.; Lohmer, G.; Reetz, M. T.; Kragl, U. J. Cat. 1999, 183, 163. (44) Datta, A.; Ebert, K.; Plenio, H. Organometallics 2003, 22, 4685. (45) Kleij, A. W.; Gossage, R. A.; Jastrzebski, J. T. B. H.; Boersma, J.; van Koten, G. Angew. Chem., Int. Ed. 2000, 39, 176. (46) Aerts, S.; Weyten, H.; Buekenhoudt, A.; Gevers, L. E. M.; Vankelecom, I. F. J.; Jacobs, P. A. Chem. Commun. 2004, 710. (47) Keraani, A.; Renouard, T.; Fischmeister, C.; Bruneau, C.; Rabiller-Baudry, M. ChemSusChem 2008, 927. (48) Schoeps, D.; Buhr, K.; Ebert, K.; Plenio, H. Chem.;Eur. J. 2009, 14, 2960. (49) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.;Eur. J. 2006, 12, 5142. (50) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. (51) Sashuk, V.; Schoeps, D.; Plenio, H. Chem. Commun. 2009, 770.

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Scheme 1. Syntheses of (NHC)Pd(allyl)Cl Complexes 3a, 3b, and 5a

a Reagents and conditions: (a) NaI, Cy2NH, acetone/dmf, 80 °C, 93%; (b) KOtBu, [PdCl(allyl)]2, THF, 86%; (c) KOtBu, [PdCl(cinnamyl)]2, THF, 54%.

The use of cyclohexyl substituents instead of long alkyl chains is beneficial, as the resulting salts (and later the Pd complexes) are microcrystalline powders rather than oily liquids (which tend to be formed with long n-alkyl chains). We also employed the imidazolium salt 4, previously reported,48 which is characterized by eight cyclohexyl groups. The enlarged imidazolinium salts 1 and 4 were reacted along the standard Nolan procedures,50,52 resulting in the respective (NHC)Pd(allyl)Cl) and (NHC)Pd(cinnamyl)Cl) complexes 3a, 3b, and 5. The (NHC)Pd(allyl)Cl complex 5 is characterized by the presence of four ortho-methyl groups and by four bulky CH2NCy2 units in the meta positions. While it is well-known that bulky isopropyl groups (rather than methyl groups) in the ortho position lead to more active “(NHC)Pd” catalysts, we were hoping that the lack of bulk in the ortho position can be compensated by bulky meta substituents. A comparison of two mass-tagged NHC ligands with the standard isopropyl-substituted NHC ligand (391 Da) shows that the molecular mass is doubled in ligand 2 (778 Da) and almost tripled in ligand 4 (1081 Da) (Scheme 2). Catalytic Activity of 3a, 3b, and 5 in the Suzuki-Miyaura Coupling. The activity of the modified complexes 3a, 3b, and 5 was tested in the Suzuki coupling and in BuchwaldHartwig amination reactions.50 Compared to complexes 3a and 3b the activity of 5 in various Suzuki coupling reactions is modest. The data of an extended reactivity study of complexes 3a and 3b in the Suzuki coupling of aryl bromides and chlorides are summarized in Table 1. It is apparent from these data that 3b, with a cinnamyl ligand, is catalytically more active than 3a, with an allyl group. This is in accord with observations made by Nolan.50 Catalytic Activity of 3b in the Buchwald-Hartwig Amination. It is known from the work of Nolan that the differences in reactivity between (NHC)Pd(allyl)Cl and (NHC)Pd(cinnamyl)Cl complexes in Buchwald-Hartwig amination reactions are pronounced.50 We therefore tested only complex 3b. Initially we used the Nolan recipe, which relies on the use (52) Navarro, O.; Nolan, S. P. Synthesis 2006, 366.

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Schoeps et al.

Scheme 2. Normal and the Two Enlarged NHC Ligands 2 and 4

Table 1. Suzuki-Miyaura Coupling of Aryl Chlorides Using Precatalysts 3a and 3b

Table 2. Buchwald-Hartwig-Amination Using Complex 3b

Conditions: 0.25 mmol of substrate, 0.26 mmol of amine, 0.28 mmol of base, catalyst: 1 mol % 3b, 5 mL of solvent, T = 40 °C, conversion determined via GC, Lihexa: 0.5 M in THF, freshly prepared by addition of nBuLi to an excess of 1,1,1,3,3,3-hexamethyldisilazane in THF at -78 °C.

Table 3. Solvent-Resistant Nanofiltration of (NHC)Pd Complexes

Conditions: 0.25 mmol of substrate, 0.26 mmol of boronic acid, 0.28 mmol of KOtBu, degassed isopropyl alcohol, 40 °C. Conversion determined via GC. aPrecatalyst 3a. bPrecatalyst 3b.

of DME solvent together with KOtBu as the base (Table 2).50 However, significantly better results were obtained under the “Caddick conditions” in THF with LiN(SiMe3)2 as the base.53 In conclusion, the excellent activity of complex 3b was demonstrated, and we next probed the retention properties of this complex in the solvent-resistant nanofiltration. (53) Cawley, M. J.; Cloke, F. G. N.; Fitzmaurice, R. J.; Pearson, S. E.; Scott, J. S.; Caddick, S. Org. Biomol. Chem. 2008, 6, 2820.

(NHC)PdCl(cinnamyl) Complex 3b in the Solvent-Resistant Nanofiltration. Several nanofiltration experiments were carried out to evaluate the retention properties of complex 3b (Table 3). In a first experiment the turbid reaction mixture resulting from the coupling of 4-bromoacetophenone with phenylboronic acid in isopropyl alcohol was directly transferred into the nanofiltration reactor. Five bars of pressure was applied to result in a permeate flow of 0.3 mL/min. This is 5 times lower than the flux observed with toluene (1.6 mL/min). It is likely that a lower degree of swelling of the

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membrane with isopropyl alcohol is responsible. Following the nanofiltration process, the permeate was evaporated and the Pd content of the remaining product determined as 323 ppm. This extremely high value indicates negligible retention of the catalyst complex by the membrane. It is likely that these problems originate from precipitated salts formed in the cross-coupling reaction on the membrane. Such solids easily lead to the mechanical abrasion of the dense 10 μm thick PDMS membrane layer responsible for the catalyst retention.54 In order to avoid this, prior to the next nanofiltration experiment all solids were filtered off using a G3 filter frit. The clear solution was passed through the nanofiltration membrane, resulting in virtually the same flow (0.25 mL/min) as before. However, after evaporation of the permeate and ICP analysis of the residue only 15 ppm Pd was found in the product. This corresponds to a 97% retention of the Pd complex. For the next experiment a 0.05 mol % loading of complex 3b was applied. The lower initial loading with Pd catalyst also led to a lower Pd content (8 ppm, 97% retention) in the product after evaporation of the permeate solvent. In order to further decrease the residual palladium, we next used a double-filtration experiment in which the permeate from the first nanofiltration underwent a second nanofiltration. When applying a 0.1 mol % loading of complex 3b, the residual Pd content in the product is below the 5 ppm detection threshold, which in this run corresponds to a Pd retention in excess of 99%. In the next experiment we tested whether the (NHC)Pd complexes dissolved in the THF solution from the amination reaction can also be separated efficiently. We know from the screening experiments that 0.1 mol % is sufficient to effect full conversion. Nonetheless, we deliberately overloaded the reaction mixture with catalyst to find out whether extremely large amounts of complex are also separated efficiently. The transmembrane flow of THF solvent is significantly higher (2.5 mL/min) than with isopropyl alcohol. The better incorporation of THF into the membrane polymer leads to more swelling of the membrane and consequently a more open membrane structure. A 1 mol % loading corresponds to almost 4000 ppm of Pd in the product in the absence of any Pd retention. The 3.5 ppm of Pd finally detected in the coupling product is indicative of an excellent (>99.9%) Pd retention (entry 4, Table 3). Another amination reaction was studied, again with high catalyst loading. The observed retention of 99.5% is very good and corresponds to a Pd level of 25 ppm (entry 5, Table 3). The efficiency of the double-filtration experiment also demonstrates that the residual Pd content found in the product should be due to small amounts of (NHC)Pd species (the precise nature of the complex 3b following the activation step is not known) permeating the membrane. It can thus be excluded that small Pd complexes resulting from the decomposition of the initial (NHC)Pd complex are formed to a significant extent since such complexes would easily penetrate the NF membrane, and a double nanofiltration would lead to no improvement over a single nanofiltration pass.

Summary and Conclusions We have demonstrated that (NHC)Pd complexes with a molecular mass of around 1000 g/mol can be efficiently (54) Ebert, K. Unpublished observations .

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separated from the products of Suzuki and BuchwaldHartwig coupling with a molecular mass of 200-250 g/mol by solvent-resistant nanofiltration. These complexes combine excellent catalytic activity with excellent retention properties, especially in THF solvent. The residual Pd content in the coupling products is between 3.5 and 25 ppm. The singlepass Pd retention in the solvent-resistant nanofiltration is in excess of 97% and can be increased to >99.9% in a doublefiltration experiment. The improved Pd retention in the double-filtration experiment shows that the residual Pd in the products does not originate from fragmented smallmolecule Pd complexes, but from intact Pd complexes coordinated to the mass-tagged NHC ligand.

Experimental Section General Procedures. All chemicals were purchased as reagent grade from commercial suppliers and used without further purification, unless otherwise noted. All reactions involving palladium complexes were performed under an atmosphere of argon. The solvents were purchased as ACS reagent grade and dried by passing through a column with dry Al2O3 with argon pressure. 1H NMR, 13C NMR, and 31P NMR spectra were recorded on a Bruker DRX 500 at 500 MHz (1H) and 126 MHz (13C), respectively, and on a Bruker DRX 300 at 300 MHz (1H) and 75 MHz (13C). The chemical shifts are given in parts per million (ppm) on the delta scale (δ) and are referenced to tetramethylsilane (1H, 13C NMR = 0.0 ppm). Abbreviations for NMR data: s=singlet; d=doublet; t=triplet; q= quartet; sep=septet; m=multiplet; bs=broad signal. Materials. For the retention of catalysts, composite membranes from GKSS consisting of a technical nonwoven, porous layer of poly(acrylonitrile) and on top of it an about 5 μm thick layer of poly(dimethylsiloxane) (PDMS), which was thermally and radiationally cross-linked, were used.55 The membranes are referred to as PAN/PDMS membranes. The membrane was conditioned for several hours in isopropyl alcohol or in THF for swelling. Prior to the nanofiltration process, the membrane was inserted into a Millipore cell (300 mL, pmax =6 bar). Filtration. After the coupling reaction is finished, the G3-fritfiltered reaction mixture was poured into the Millipore cell. After closing the cell and applying pressure (5 bar argon), permeate was collected in a flask. The coupling product was obtained from the permeate after evaporation of the volatiles and weighed. Batch experiments and catalyst screening: The reaction yield was determined via gas chromatography on a CP-Sil 8 CB column (15 m, di =0.25 mm, Varian) with a PerkinElmer Clarus 500 GC AutoSystem or via NMR spectroscopy on a Bruker DRX 300 spectrometer at 300 MHz (1H NMR). Analysis. The Pd analysis was performed with ICP-OES on a Perkin-Elmer Optima 2000 DV spectrometer at CAL GmbH & Co. KG, Darmstadt. Membrane characterization. Membrane stamps with a diameter of 7.5 cm were installed in test cells with an effective membrane area of 34 cm2. For quality control of the membranes the oxygen and nitrogen flows were measured at a pressure difference of 4 bar with a soap bubble meter. For each membrane stamp 10 measurements were performed, which were used for the calculation of an average flux. With these average fluxes the oxygen/nitrogen selectivity was calculated. Only stamps with an oxygen/nitrogen selectivity of 2.1 were used for retention experiments. N,N-Bis(4-((N-dicyclohexyl)aminomethyl)-2,6-diisopropylph enyl)-4,5-dihydro-1H-imidazolium iodide (2 3 HI). A mixture of N,N-bis(4-chloromethyl-2,6-diisopropylphenyl)-4,5-dihydro1H-imidazolium chloride (1) (1.00 g, 1.91 mmol, 1 equiv), NaI (55) Schmidt, M.; Peinemann, K. V.; Scharnagl, N.; Friese, K.; Schubert, R. Strahlenchemisch modifizierte Silikonkompositmembran f€ ur die Ultrafiltration. German Patent Application DE 96/00336, 1996.

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(2.86 g, 19.1 mmol, 10 equiv), and Cy2NH (4 mL, 19.1 mmol, 10 equiv) was suspended in a mixture of acetone (50 mL) and DMF (50 mL). The mixture was stirred at 80 °C for 12 h. After cooling to room temperature and addition of CH2Cl2 (200 mL) and NaOH solution (2 N, 200 mL), the organic layer was separated and extracted with water (200 mL, two times). The organic layer was separated, dried over MgSO4, and filtered, and the volatiles were evaporated under reduced pressure. To the remaining oily residue was added pentane (50 mL), and a solid was formed and filtered off. After washing with pentane, drying of the solid in vacuo afforded 1 (1.28 g, 1.77 mmol, 93% yield) as a fine colorless powder. 1H NMR (300 MHz, d6-DMSO): δ 9.36 (s, 1H, CHimidazolium), 7.37 (s, 4H, CHaryl), 4.50 (s, 4H, CH2-imidazolium), 3.78 (s, 4H, CH2-benzyl), 3.05 (h, 3J = 7 Hz, 4H, CHisopropyl), 1.72-0.99 (m, 44H, CHcyclohexyl), 1.32 (d, 3J = 7 Hz, 12H, CH3-isopropyl), 1.16 (d, 3J = 7 Hz, 12H, CH3-isopropyl) ppm. 13C NMR (75 MHz, CDCl3): δ 160.6, 146.7, 145.7, 128.2, 123.4, 57.8, 54.0, 49.4, 31.9, 28.5, 26.3, 26.1, 26.0, 25.4, 25.3, 23.8 ppm. HR-MS: calculated for C53H85N+ 4 777.6775, found 777.6774. (1)Pd(allyl)Cl (3a). Imidazolinium salt 1 3 HI (270 mg, 0.3 mmol, 1 equiv) and [PdCl(allyl)]2 (55 mg, 0.15 mmol, 0.5 equiv) were dissolved in THF (10 mL). After addition of KOtBu (34 mg, 0.3 mmol, 1 equiv) and stirring at -78 °C for 30 min under an atmosphere of argon, the mixture was allowed to warm to room temperature during 60 min. Removal of the solvent in vacuo and washing of the remaining dark solid with pentane afforded the crude product, which was purified by column chromatography (silica, cyclohexane/ethyl acetate = 1:1). Removal of the volatiles in vacuo afforded complex 3a (250 mg, 0.26 mmol, 86% yield) as a pale yellow powder. 1H NMR (300 MHz, CDCl3): δ 7.20 (s, 2H, CHaryl), 7.19 (s, 2H, CHaryl), 5.29 (h, 3J = 6.8 Hz, 0.5H, CHallyl), 4.59 (h, 3J = 6.8 Hz, 1H, CHallyl), 4.37 (d, 3J = 6.8 Hz, 1H, CHallyl), 3.66 (h, 3J = 6.8 Hz, 0.5H, CHallyl), 4.07-3.96 (m, 4.5H, CH2-imidazolium, CHallyl), 3.73 (s, 4H, CH2-benzyl), 3.60-3.40 (m, 4.5H, CH3-isopropyl, CHallyl), 3.07 (d, 2J = 12.5 Hz, 1H, CHallyl), 2.50 (m, 4H, CHcyclohexyl), 1.760.89 (m, 64H, CH2-cyclohexyl, CH3-isopropyl) ppm. 13C NMR (75 MHz, CDCl3): δ 213.0, 145.5, 145.1, 142.9, 133.6, 122.5, 111.9, 57.3, 56.8, 53.2, 48.9, 31.2, 27.5, 26.0, 25.8, 25.6, 25.4, 23.2, 23.1, 23.0, 22.8 ppm. IR (KBr): ν 2961, 2927, 2851, 1465, 1447, 1424, 1289, 1259, 1118 cm-1. ESI-MS: m/z 923.8 (M•+ - Cl), 778.0 (M•+ - Pd(allyl)Cl). Anal. Calcd for C56H89N4ClPd (960.2): C, 70.05; H, 9.34; N, 5.83. Found: C, 69.73; H, 8.81; N, 6.05. (1)Pd(cinnamyl)Cl (3b). Imidazolinium salt 1 3 HI (420 mg, 0.464 mmol, 1 equiv) and [Pd(cinnamyl)Cl]2 (120 mg, 0.232 mmol, 0.5 equiv) were dissolved in THF (30 mL). After addition of KOtBu (52 mg, 0.464 mmol, 1 equiv) and stirring at -78 °C for 30 min under an atmosphere of argon, the mixture was allowed to warm to room temperature during 120 min. Removal of the solvent in vacuo and washing of the remaining dark orange solid with pentane afforded the crude product, which was purified by column chromatography (silica, cyclohexane/ethyl acetate = 10:1). Removal of the volatiles in vacuo afforded complex 3b (258 mg, 0.25 mmol, 54% yield) as an orange powder. 1H NMR (300 MHz, CDCl3): δ 7.28-6.99 (m, 9H, CHaryl), 5.72 (h, 3J = 6.8 Hz, 0.75H, CHallyl), 5.00 (h, 3J = 6.8 Hz, 0.75H, CHallyl), 4.80 (d, 3J = 11.4 Hz, 0.75H, CHallyl), 4.12-4.96 (m, 5.75H, CHallyl, CH2-imidazolinium), 3.69 (s, 4H, CH2-benzyl), 3.47-3.34 (m, 5H, CH3-isopropyl, CHallyl), 2.97 (d, 2J = 12.5 Hz, 1H, CHallyl), 2.44 (m, 4H, CHcyclohexyl), 1.76-0.89 (m, 64H, CH2-cyclohexyl, CH313 isopropyl) ppm. C NMR (75 MHz, CDCl3): δ 142.9, 136.5, 127.8, 127.4, 127.1, 127.0, 125.5, 122.5, 103.9, 87.6, 60.9, 56.8, 53.1, 51.8, 48.9, 31.1, 28.7, 27.4, 25.8, 25.5, 25.3, 23.3, 23.1, ppm. IR (KBr): ν 2961, 2926, 2850, 1447, 1260, 1102, 1021, 802 cm-1. ESI-MS: m/z 999.6 (M•+ - Cl), 778.1 (M•+ - Pd(cinnamyl)Cl). Anal. Calcd for C62H93N4ClPd (1036.3): C, 71.88; H, 9.05; N, 5.41. Found: C, 71.88; H, 8.93; N, 5.17. (4)Pd(allyl)Cl. Imidazolinium salt 4 (558 mg, 0.50 mmol, 2.0 equiv) and [Pd(allyl)Cl]2 (91 mg, 0.25 mmol, 1.0 equiv) were

Schoeps et al. dissolved in THF (10 mL) and cooled to -78 °C. After addition of KOtBu (59 mg, 0.53 mmol, 2.1 equiv) and stirring for 30 min, the mixture was allowed to warm to room temperature while the color changed from yellow to brownish-black. Evaporation of the volatiles under reduced pressure and short column chromatography of the remaining solid (CH2Cl2/pentane, 1:1) afforded (NHC)Pd(allyl)Cl 5 (258 mg, 0.21 mmol, 82%) as a grayish powder. 1H NMR (500 MHz, CDCl3): δ 5.29 (s, 2H, CHallyl), 4.68 (h, 3J = 6.3 Hz, 1H, CHallyl), 3.90 (s, 4H, NCH2-imidazolin), 3.86-3.69 (m, 9H, CH2-benzyl, CHallyl), 3.22 (d, 3J = 6.3 Hz, 1H, CHallyl), 2.51 (s, 6H, CH3-aryl), 2.50 (s, 6H, CH3aryl), 2.39 (m, 8H, CH-cyclohexyl), 1.78-1.00 (m, 80H, Cy) ppm. 13C NMR (125 MHz, CDCl3): δ 211.2, 139.6, 136.4, 135.4, 135.3, 114.3, 72.3, 55.6, 53.4, 52.0, 49.1, 44.8, 32.4, 32.1, 26.8, 26.3, 16.0, 15.9 ppm. Anal. Calcd for C76H123N6ClPd (1262.7): C, 72.29; H, 9.82; N, 6.66. Found: C, 72.07; H, 10.19; N, 6.13. Suzuki-Miyaura Cross-Coupling and Subsequent Organophilic Nanofiltration: Coupling of 4-Bromoacetophenone with Phenylboronic Acid, 0.1 mol % Complex 3a. 4-Bromoacetophenone (1.28 g, 10.5 mmol) and phenyl boronic acid (1.99 g, 10.0 mmol) were dissolved in degassed isopropyl alcohol (240 mL) in a 250 mL Schlenk flask under argon. Pd complex 3a (9.2 mg, 9.58 μmol, 0.1 mol %) and KOtBu (1.23 g, 11 mmol) were added, and the reaction vessel was stirred at 40 °C for 1.5 h. After cooling the reaction mixture to room temperature and filtration of the formed salts with a glass sinter frit, the solution was poured into the Millipore cell and the nanofiltration started. Nanofiltration: membrane, GKSS PDMS 05/069 #KB100; flow, 0.25 mL/min (isopropyl alcohol); Δp, 5 bar (argon); permeate, 60 mL (25%); retentate, 180 mL (75%). Total yield (4-phenylacetophenone): 99% (GC). Isolated yield by SRNF: 495 mg (25%). Theoretical loading of Pd by 0% retention: 519 ppm. Found palladium in product: 15 ppm. Catalyst retention at the membrane: 97% Suzuki-Miyaura Cross-Coupling and Subsequent Organophilic Nanofiltration: Coupling of 4-Bromoacetophenone with Phenylboronic Acid, 0.05 mol % Complex 3b. 4-Bromoacetophenone (1.28 g, 10.5 mmol) and phenylboronic acid (1.99 g, 10.0 mmol) were dissolved in degassed isopropyl alcohol (200 mL) in a 250 mL Schlenk flask under argon. Pd complex 3b (5 mg, 8.82 μmol, 0.05 mol %) and KOtBu (1.23 g, 11 mmol) were added, and the reaction vessel was stirred at 40 °C for 17 h. After cooling the reaction mixture to room temperature, the formed salts were filtered off. The filtrate was diluted with 100 mL of isopropyl alcohol and poured into the Millipore cell to start the nanofiltration. Nanofiltration: membrane, GKSS PDMS 05/069 #KB118; flow, 0.20 mL/min (isopropyl alcohol); Δp, 5 bar (argon); permeate, 65 mL (22%); retentate, 235 mL (78%). Total yield (4-phenylacetophenone): 99% (GC). Isolated yield by SRNF: 414 mg (21%). Theoretical loading of Pd by 0% retention: 414 ppm. Found palladium in product: 8 ppm. Catalyst retention at the membrane: 97%. Suzuki-Miyaura Cross-Coupling and Subsequent Double Nanofiltration: Coupling of 1-Bromonaphthaline with 1-Naphthylboronic Acid, 0.1 mol % Complex 3b. 1-Bromonaphthaline (1.806 g, 10.5 mmol) and 1-naphtylboronic acid (2.071 g, 10.0 mmol) were dissolved in degassed isopropyl alcohol (250 mL) in a 250 mL Schlenk flask under argon. The Pd complex 3b (11 mg, 10.6 μmol, 0.1 mol %) and KOtBu (1.23 g, 11 mmol) were added, and the reaction vessel was stirred at 40 °C for 1 h. After cooling the reaction mixture to room temperature, the formed salts were filtered off. The filtrate was poured into the Millipore cell to start the nanofiltration. The resulting permeate was collected and subjected to another filtration process with a fresh membrane. First nanofiltration: membrane, GKSS PDMS 05/069 #KB104; flow, 0.25 mL/min (isopropyl alcohol); Δp, 5 bar (argon); permeate, 125 mL (50%); retentate, 125 mL (50%). Second nanofiltration: membrane, GKSS PDMS 05/069

Article #KB103; flow, 0.25 mL/min (isopropyl alcohol); Δp, 5 bar (argon); permeate, 65 mL (52%); retentate, 60 mL (48%). Total yield (1,10 -binaphthyl): 99% (GC). Isolated yield by SRNF: 277 mg (11%). Theoretical loading of Pd by 0% retention: 444 ppm. Found palladium in product: 99%. Buchwald-Hartwig Amination and Subsequent Double Nanofiltration: Coupling of 4-Bromobenzonitrile with Cy2NH, 1 mol % Complex 3b. 4-Bromobenzonitrile (325 mg, 1.785 mmol) and Cy2NH (388 mg, 2.142 mmol, 426 μL) were dissolved in degassed THF (210 mL) in a 250 mL Schlenk flask under argon. The Pd complex 3b (18.5 mg, 17.9 μmol, 1 mol %) and Lihexa (0.5 M solution in THF, 3.93 mL, 1.96 mmol) were added, and the reaction vessel was stirred at 40 °C for 1 h. After cooling the reaction mixture to room temperature the solution was poured into the Millipore cell to start the nanofiltration. The resulting permeate was collected and subjected to a second filtration process with a fresh membrane. First nanofiltration: membrane, GKSS PDMS 05/069 #KB105; flow, 2.5 mL/min (THF); Δp, 5 bar (argon); permeate, 140 mL (67%); retentate, 70 mL (33%). Second nanofiltration: membrane, GKSS PDMS 05/069 #KB117; flow, 2.25 mL/min (THF); Δp, 5 bar (argon); permeate, 70 mL (50%); retentate, 70 mL (50%). Total yield (N,N-dicyclohexyl-4-nitrile-aniline): 97% (GC). Isolated yield by SRNF: 225 mg (45%). Theoretical loading of Pd by 0% retention: 3769 ppm. Found palladium in product: 3.5 ppm. Catalyst retention at the membrane: 99.9%.

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Buchwald-Hartwig Amination and Subsequent Organophilic Nanofiltration: Coupling of 4-Chloroanisol with 3,5-Dimethylaniline, 1 mol % Complex 3b. 4-Chloroanisol (1.40 g, 9.84 mmol, 1.20 mL) and 3,5-dimethylaniline (1.43 g, 11.81 mmol, 1.48 mL) were dissolved in degassed THF (230 mL) in a 250 mL Schlenk flask under argon. The Pd complex 3b (102 mg, 98.4 μmol, 1 mol %) and Lihexa (0.6 M solution in THF, 18.04 mL, 10.82 mmol) were added, and the reaction vessel was stirred at 40 °C for 4 h. After cooling the reaction mixture to room temperature the solution was poured into the Millipore cell to start the filtration process. The resulting permeate was collected and subjected to a second filtration process with a fresh membrane. First nanofiltration: membrane, GKSS PDMS 05/069 #KB112; flow, 2.0 mL/min (THF); Δp, 5 bar (argon); permeate, 60 mL (26%); retentate, 170 mL (74%). Total yield (3,5dimethyl-N-(4-methoxyphenyl)aniline): 86% (GC). Isolated yield by SRNF: 243 mg (11%). Theoretical loading of Pd by 0% retention: 4681 ppm. Found palladium in product: 25 ppm. Catalyst retention at the membrane: 99.5%.

Acknowledgment. This work was supported by the BMBF project (01R/05111): “Organophile Nanofiltration f€ ur die nachhaltige Produktion in der Industrie”. Supporting Information Available: This material is available free of charge via the Internet at http://pubs.acs.org.