Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic

Review pubs.acs.org/CR

Immobilization of N‑Heterocyclic Carbene Compounds: A Synthetic Perspective Rui Zhong, Anja C. Lindhorst, Florian J. Groche, and Fritz E. Kühn* Molecular Catalysis, Department of Chemistry and Catalysis Research Center, Technical University of Munich, Lichtenbergstrasse 4, 85747 Garching bei München, Germany ABSTRACT: Over the course of the past 15 years the success story of N-heterocyclic carbene (NHC) compounds in organic, inorganic, and organometallic chemistry has been extended to another dimension. The immobilization of NHC compounds, undergoing continuous diversification, broadens their range of applications and leads to new solutions for challenges in catalytic and synthetic chemistry. This review intends to present a synthetic toolkit for the immobilization of NHC compounds, giving the reader an overview on synthetic techniques and strategies available in the literature. By individually summarizing and assessing the synthetic steps of the immobilization process, a comprehensive picture of the strategies and methodologies for the immobilization of NHC compounds is presented. Furthermore, the characterization of supported NHC compounds is discussed in detail in order to set up necessary criteria for an in-depth analysis of the immobilized derivatives. Finally, the catalytic applications of immobilized NHC compounds are briefly reviewed to illustrate the practical use of this technique for a broad variety of reaction types.

CONTENTS 1. Introduction 2. Synthetic Strategies for the Immobilization of NHeterocyclic Carbene Compounds 2.1. Formation of the Functionalized NHC Moiety 2.1.1. Hydroxyl Functionalized NHC Compounds 2.1.2. Alkenyl Functionalized NHC Compounds 2.1.3. Trialkoxysilyl Functionalized NHC Compounds 2.1.4. Carboxyl Functionalized NHC Compounds 2.1.5. Alkynyl Functionalized NHC Compounds 2.1.6. Amine Functionalized NHC Compounds 2.1.7. Multitopic NHC Compounds 2.1.8. Soluble Polymer Functionalized NHC Compounds 2.1.9. NHC Compounds Bearing Miscellaneous Functional Groups 2.2. Heterogenization of NHC Compounds 2.2.1. Solid Phase Synthesis 2.2.2. Covalent Grafting 2.2.3. Self-Supporting Methods 2.2.4. Formation of NHC Stabilized Metal NPs 2.2.5. Immobilization via Noncovalent Interactions 2.3. Metalation of NHC Precursors 2.3.1. NHC−Pd Complexes © XXXX American Chemical Society

2.3.2. NHC−Ru Complexes 2.3.3. Coinage Metal NHC Complexes 2.3.4. Group 9 Metal (Rh, Ir) NHC Complexes 2.3.5. Miscellaneous Metal−NHC Complexes 3. Characterization of Immobilized NHC Compounds 3.1. Characterization of Supported NHC Moieties 3.2. Characterization of Supporting Materials 3.2.1. Characterization of Soluble Supporting Materials 3.2.2. Characterization of Insoluble Supporting Materials 3.3. Characterization Involved in Catalytic Reactions 4. Catalytic Applications of Immobilized NHC Compounds 4.1. General Considerations 4.2. Cross-Coupling Reactions 4.2.1. Suzuki−Miyaura Reaction 4.2.2. Mizoroki−Heck Reaction 4.2.3. Sonogashira Reaction 4.2.4. Miscellaneous Coupling Reactions 4.3. Olefin Metathesis 4.3.1. Ring Closing Metathesis 4.3.2. Cross Metathesis 4.4. Hydrosilylation 4.5. Cyanosilylation 4.6. Hydrogenation 4.7. Miscellaneous Catalytic Reactions

B B B C E F H I I I J K M O T AC AO AR AW AX

AZ BB BD BE BF BF BG BH BH BI BJ BJ BK BK BM BO BO BP BP BS BT BT BT BU

Received: September 13, 2016

A

DOI: 10.1021/acs.chemrev.6b00631 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews 5. Conclusion and Perspectives Author Information Corresponding Author ORCID Notes Biographies Acknowledgments Abbreviations References

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functionalized support or self-support (section 2.2.3). The latter encompasses various methods where NHC precursors or NHC metal complexes are immobilized concomitantly in the construction of the supporting material. The resulting supports vary strongly in nature, including organic polymers, coordination polymers, MOFs, and silica materials. Further strategies for the heterogenization of NHC compounds covered by this review are the stabilization of metal nanoparticles by NHCs (section 2.2.4) and the immobilization via noncovalent interactions including electrostatic interactions and π−π stacking (section 2.2.5). Section 2.3 covers the metalation of NHC precursors and is organized according to the elements used, focusing on the metalation of specifically functionalized and/or heterogenized NHC precursors. Furthermore, characterization is a crucial step to evaluate the immobilization process. In order to provide necessary criteria for an in-depth analysis of the immobilized derivatives, section 4 is directed toward analytic techniques used for the characterization of supported NHC compounds. In section 5 catalytic applications of immobilized NHC complexes are briefly reviewed. To avoid possible redundancies with other reviews in this field,3,9,13−16,19 all examples are summarized in a tabular manner according to the reaction types. Moreover, section 5 also highlights possible research directions for future developments toward industrially applicable catalysts comparing the immobilized catalysts and their corresponding homogeneous analogues. It should be emphasized that not only NHC metal complexes, but also free NHCs and NHC adducts, lie within the scope of this review. Due to the fact that imidazolium-based ionic liquids may also be employed as NHC precursors and the applied synthetic methods overlap with those of supported NHC compounds, several representative examples of supported ionic liquids are discussed in corresponding sections to provide a broader database for consideration.20 Since many publications describe the preparation of immobilized NHC precursors for further in situ generation of free NHCs or NHC metal complexes, the term “immobilized NHC compound” in this article not only refers to free NHCs and their complexes but also encompasses NHC precursors, in particular imidazolium and imidazolinium salts. In line of this also supported ionic liquid phases (SILPs) are considered within this article as they constitute potential precursors of free NHCs or NHC metal complexes. However, the exact NHC compound class will be mentioned whenever necessary. Furthermore, the carbene atom as well as its protonated analogue will be denoted as the C2 atom.

BU BW BW BW BW BW BW BW BX

1. INTRODUCTION The immobilization (heterogenization) of homogeneous catalysts is an attractive and versatile tool to achieve recoverable and recyclable catalysts.1−3 It represents a resurging research field, which is targeted frequently and has shown constant development in recent years. N-Heterocyclic carbenes (NHCs) rank among the most useful ligands for tuning various properties of metal complexes for applications in both academically interesting and industrially important processes.4−12 In this context, the immobilization of NHC compounds has become a promising area of research, experiencing continuous diversification. Since the first publications on immobilized NHC compounds in 2000, close to 300 research papers have been published on this topic. Regarding the short time span of less than 16 years, this demonstrates the rapid growth in interest especially within the past five years (Figure 1). To date, three review articles on this subject have been published.13−15 However, these articles are limited to the enumeration of the most representative advances before 2013. A detailed insight into synthetic strategies and characterization of immobilized NHC compounds is not included. Several reviews also address single aspects of the immobilization of NHC compounds as parts of broader topics, but are not directed toward this specific area.6,16−19 In view of this state of the art, a synthetic toolkit for the immobilization of NHC compounds is presented in this article based on a comprehensive review on the achievements made in this field. Since to date there is no single report particularly focused on synthetic techniques and strategies, this review aims at analyzing all published examples up to 2016 with regard to synthetic methods in order to provide a systematic insight on availability and feasibility of immobilized NHC compounds. In general, the synthesis of immobilized NHC compounds can be divided into the three correlative steps: formation of the NHC moiety, metalation, and heterogenization (Figure 2). Since all synthetic steps can be independent or combined, the correlation between the three steps can be viewed as a triangle relation, in which the selection of the initial step will certainly exert influence on the following steps, thus determining the immobilization strategy to be employed. In this sense, section 2 will cover in detail the synthesis of immobilized NHC compounds in three subsections corresponding to the three basic steps. The formation of the NHC moiety (section 2.1) includes the synthesis of functionalized NHC precursors and metal complexes suitable for immobilization. The heterogenization (section 2.2) can be achieved employing one of the following basic strategies: solid phase synthesis (section 2.2.1), which comprises the synthesis of the NHC moiety directly on the supporting material either by quaternization or cyclization, covalent grafting (section 2.2.2), i.e. the formation of a covalent bond between a preformed NHC compound and a suitably

2. SYNTHETIC STRATEGIES FOR THE IMMOBILIZATION OF N-HETEROCYCLIC CARBENE COMPOUNDS 2.1. Formation of the Functionalized NHC Moiety

The most widely used method to obtain NHC moieties is through their imidazolium precursors. For immobilization purposes, different functionalities such as hydroxyl, carboxyl, alkenyl, and alkoxysilyl groups are commonly introduced to NHC moieties through the preparation of the respective imidazolium salts (Figure 3). These can be obtained by either quaternization of N-substituted imidazoles or multicomponent cyclization. In this section, an overview of the functionalized imidazolium precursors of NHC compounds will be given B


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Figure 1. Number of annually published reports on immobilized NHC compounds as of August 2016.

diamines. Anilines bearing iodide, bromide, hydroxyl, and allyl groups have been reported as suitable starting materials. For this synthetic strategy, the accessibility of the respective amines or imines and the tolerance of the final ring-closing step toward functional groups have to be considered. In the following section, synthetic strategies for functionalized NHC precursors will be summarized according to their respective functionality and substitution pattern, i.e. substitution at N- and/or C-positions. 2.1.1. Hydroxyl Functionalized NHC Compounds. The hydroxyl group is a synthetically flexible group, which not only can form esters and ethers, but also can be further transformed into other functionalities such as carbonyl, nitrile, and halide groups. In view of this, the preparation of hydroxyl functionalized NHC ligands for immobilization purposes appears as a reasonable choice. Reactions between hydroxyl functionalized primary alkyl halides and N-substituted imidazoles have been reported to prepare a series of hydroxyl functionalized mono-NHC precursors 1−5 with varying chain lengths and counterions (Scheme 3).24−29 This type of synthesis, which is used to

according to the introduced functionalities and the synthetic methods. Direct quaternization of N-substituted imidazoles or imidazolines with alkyl or aryl halides (or triflate derivatives) is the most straightforward method to prepare imidazol(in)ium salts in a single step.5,21,22 Alkyl halides, especially primary alkyl halides, can effectively react with various N-substituted imidazoles or imidazolines (from here on, the reactions described for imidazoles also comprise the use of imidazolines) under mild conditions to afford the quaternized products in good to excellent yields. Furthermore, the following isolation of the products from the reaction mixture is relatively easy as the synthesized imidazolium salts usually precipitate from the reaction mixture and can be collected by filtration. More importantly, alkyl halides are readily available, as many of them can be purchased from commercial suppliers or easily synthesized and modified. Hence, the use of alkyl halides to prepare functionalized NHC precursors for immobilization is a feasible and effective way. Basically, two approaches can be followed for this type of NHC ligand synthesis: either functionalized alkyl halides are reacted with N-substituted imidazoles or N-functionalized imidazoles react with alkyl halides as depicted in Scheme 1. Since functionalized alkyl halides are much more easily obtained than functionalized imidazoles in most cases, the former method is more often employed than the latter. In contrary to the direct quaternization of N-substituted imidazoles, synthesis of imidazolium salts through a cyclization step is the more synthetically challenging method.5,21−23 However, it provides higher flexibility for the functionalization of NHC ligands regarding structural, steric or electronic aspects. By this method not only the N-substituents of the NHC ligand but also the backbone of the NHC ligand can be functionalized. The cyclization method, according to the definitions given by César et al.,23 can be classified by three main types depending on the final ring-closing step. Introduction of the precarbenic unit in the final step is found to be the most widely applied strategy to prepare NHC precursors for immobilization, due to its easy accessibility and high substituent tolerance (Scheme 2). In such syntheses, first nitrogen- or carbon-substituted diimines or diamines are prepared. They subsequently react with cyclization reagents to introduce the C2 carbon and hence form the NHC precursors. To prepare N-substituted imidazolium precursors, functionalized amines (e.g., p-substituted aniline) are typically reacted with glyoxal (or its derivatives) to yield diimines or

Figure 2. Synthetic steps for the immobilization of NHC compounds. C


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Figure 3. Strategies for the formation of NHC moieties with functional groups.

Scheme 1. Direct Quaternization Approaches for the Synthesis of Functionalized Imidazolium Salts

Scheme 4. Synthesis of Hydroxyl Functionalized Bisimidazolium Salts 9−16 by Direct Quaternization33−35

Scheme 2. Cyclization Synthesis of Functionalized NHC Precursors by Introduction of the Precarbenic Unit in the Final Step

prepare imidazolium-based ionic liquids as well,30 can proceed under both solvent (e.g., THF) and solvent-free conditions, affording high yields of products in most cases. Furthermore, Lee et al.31 described the use of monotosylated PEGs, which are derived from alkyl halides, to react with 1-methylimidazole under solvent-free conditions, producing hydroxyl functionalized mono-NHC ligands 6−7 in almost quantitative yields (Scheme 3). Zhou and co-workers32 reported the synthesis of bis-hydroxyl functionalized imidazolium salt 8 by direct quaternization of 1-methylimidazole with bis(phenolic) functionalized alkyl chloride in isopropanol at 75 °C for 48 h. In addition to the mono-NHC precursors, our group also reported three different types of hydroxyl functionalized bis-imidazolium salts 9−16 for immobilization purposes (Scheme 4).33−35 The syntheses of 9−10 and 14−16 are similar to those of the abovementioned monoimidazolium salts using primary alkyl halides. The synthesis of 11−13, however, requires more rigorous

reaction conditions (up to 130 °C in a pressure tube for 1 week) as the secondary alkyl dichloride (dichloroethanol) is relatively unreactive. Notably, variation of the N-substituents and functionalization of the hydroxyl group allows electronic and steric fine-tuning of 11−13.35 Besides the use of functionalized alkyl halides, the quaternization of a hydroxyl functionalized imidazole by methyl iodide was reported by Á lvarez et al.28 for the preparation of NHC precursor 17 in high yields (Scheme 5). Apart from the quaternization approach, cyclization reactions were reported for the preparation of hydroxyl functionalized

Scheme 3. Synthesis of Hydroxyl Functionalized Imidazolium Salts 1−8 by Direct Quaternization24−29,31,32

D


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2.1.2. Alkenyl Functionalized NHC Compounds. Alkenyl compounds are versatile reactants that can, on one hand, be directly used to synthesize polymers. On the other hand, the alkenyl group can react with or be transformed into other functionalities.44,45 Therefore, the preparation of alkenyl functionalized NHC precursors also poses a strategy for the immobilization of NHC compounds. Lee and co-workers46,47 reported the preparation of vinylbenzyl functionalized NHC precursor 26 in excellent yields (97%) by direct quaternization of 1-methylimidazole and chloromethylstyrene at 50 °C in CHCl3 (Scheme 7). Furthermore, anion exchange of 26 with

Scheme 5. Synthesis of Hydroxyl Functionalized Imidazolium Salt 17 by Direct Quaternization28

NHC precursor 18−25 (Scheme 6). In these syntheses, first diimines or diamines bearing hydroxyl groups are prepared for Scheme 6. Preparation of Hydroxyl Functionalized NHC Precursors 18−25 by Cyclization36−43

Scheme 7. Preparation of Alkenyl Functionalized NHC Precursors 26−31 by Direct Quaternization of Alkenyl Functionalized Alkyl Halides and N-Substituted Imidazoles46−51

NaPF6 in acetone at room temperature afforded 27 in almost quantitative yield. Following the same strategy, also ethylimidazole can be quaternized with chloromethylstyrene at 80 °C in methanol solution affording imidazolium salt 28 after anion exchange with potassium acetate.48 Li et al.49 described the synthesis of alkenyl functionalized NHC precursor 29 in 90% yield via the direct quaternization of 1-methylimidazole with 6-bromohexyl acrylate under solvent-free conditions at 45 °C for 20 h (Scheme 7). The groups of Weck50 and Buchmeiser51 reported the direct quaternization of an imidazole or tetrahydropyrimidine with halogen functionalized norbornene (NBE) to synthesize the NBE functionalized NHC precursors 30 and 31 (Scheme 7). Both reactions were conducted in apolar solvents under reflux conditions, affording products in good to excellent yields. Furthermore, the direct quaternization of commercially available 1-vinylimidazole with

further cyclization with a ring-closing reagent (e.g., triethyl orthoformate, paraformaldehyde). With respect to the syntheses of 19−21 and 23−25, the protection of the hydroxyl groups by chlorotrimethylsilane (TMSCl) or chloro-tertbutyldimethylsilane (TBDMSCl) is reported for the cyclization step,36−41 while the preparation of 18 is described without protection of the hydroxyl groups during cyclization.42 Therefore, two more steps comprising protection and deprotection of the hydroxyl groups are required for the syntheses of 19−21 and 23−25 compared to that of 18. It should be noted that the preparation of 22 was achieved by introduction of a carbonyl functionality to the NHC backbone during precursor synthesis rather than direct attachment of the hydroxyl group.43 Thus, 22 was obtained as a mixture of the enol and keto tautomers in a 1/1 equilibrium as indicated by the 1H NMR spectroscopy. E


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various alkyl halides has been reported frequently to obtain the alkenyl functionalized NHC precursors 32−41 in yields of 76− 99% (Scheme 8).52−61 The syntheses of 32−41 proceeded

Scheme 9. Preparation of Alkenyl Functionalized NHC Precursors 43−44 and 45−47 by Transformation of the Hydroxyl Functionalized Precursors 19−20 and 23− 2436−39,41

Scheme 8. Synthesis of Alkenyl Functionalized NHC Precursors 32−42 by Direct Quaternization of Vinyl Functionalized Imidazole Compounds52−62

corresponding imidamide with dichloroethane in the presence of DIPEA.69 2.1.3. Trialkoxysilyl Functionalized NHC Compounds. Organosiloxanes, which have been widely used for surface modification as well as preparation of hybrid materials, are also intensively investigated for catalyst immobilization.70−77 It has been demonstrated that the immobilization of catalysts by covalent Si−O−Si bonds to the supporting materials can be a simple and effective process to obtain heterogenized catalysts. In this context, the preparation of organosiloxane bearing NHC precursors naturally became a practical approach for immobilization of these compounds. Since a number of organosiloxanes are commercially available, halogen substituted trialkoxysilanes are used intensively to directly quaternize Nsubstituted imidazoles or dihydroimidazoles to prepare trialkoxysilyl functionalized NHC precursors. Table 1 summarizes trialkoxysilyl functionalized imidazolium salts that were prepared by quaternization of (3-halopropyl)trialkoxysilanes and N-substituted imidazoles in good to excellent yields (58− 99%). In general, the reactions were conducted in aprotic solvents, mostly toluene or acetonitrile, under reflux conditions. Additionally, several studies described solvent-free conditions under inert atmosphere at 80−110 °C. These reactions usually resulted in higher yields than their counterparts in solution (e.g., 66, 69, and 70). Furthermore, the reaction time varies from case to case between 6 h and 5 days. Still, a time span of 24 h is sufficient for most cases. Additionally, the (3halopropyl)trialkoxysilanes are usually applied stoichiometrically or in excess in order to completely consume the imidazole substrate, obtaining a high product yield. Apart from halogen substituted trialkoxysilanes, the use of trialkoxysilyl functionalized imidazoles for the synthesis of the trialkoxysilyl functionalized NHC precursors 84−91 by quaternization with alkyl halides has also been mentioned (Scheme 11).93,107,119−123 The synthetic conditions in terms of solvents and temperatures are similar to the above-mentioned quaternization reactions. However, trialkoxysilyl functionalized

under both solvent and solvent-free conditions over a broad range of temperatures. In addition, Luo et al.62 reported the preparation of a specially designed vinyl functionalized NHC precursor 42 in moderate yield (40%) by methylation of the respective vinyl functionalized benzyltheobromine compound with methyl iodide in DMF solution at 100 °C for 20 h. Furthermore, the hydroxyl functionalized NHC precursors 19− 20 and 23−24 can also be further transformed into the alkenyl functionalized NHC precursors 43−44 and 45−47, respectively, by the reaction with norborn-5-ene-2-carboxylic chloride or methacryloyl chloride in the presence of trimethylamine (Scheme 9).36−39,41 Employing the cyclization method, the backbone functionalized alkenyl NHC precursors 48−49 as well as the biaryl Nsubstituted NHC precursors 50−54 were obtained (Scheme 10). To prepare 48 and 49, the presynthesized diimines were first functionalized with alkenyl groups through the reaction with a Grignard reagent (allyl magnesium bromide) and then reduced by sodium borohydride to obtain the alkenyl functionalized diamines. These were cyclized with triethyl orthoformate in the presence of HCl or NH4Cl, eventually producing the desired imidazolinium salts in excellent yields (80−92%).63−65 50−53 were synthesized by a similar sequence, initially introducing the alkenyl group to the diimine or diamine, which further reacted with the corresponding ringclosing reagent to form the functionalized NHC precursors in good to excellent yields (40−89%).63,66−68 A reversed strategy was used by Johnson et al., who synthesized compound 54 by Pd-catalyzed allylation of the preformed bromo-functionalized imidazolinium salt, which was received by cyclization of the F


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Scheme 10. Synthesis of Alkenyl Functionalized NHC Precursors 48−53 by Cyclization63−69

preparation of immobilized chiral Au, Rh, and Pd NHC complexes.124,125 However, in contrast to the syntheses of 97− 99, which had long reaction times at room temperature, the alkylation step of the syntheses of 102−103 was conducted under microwave irradiation in only 3 h, obtaining the products in quantitative yields. Furthermore, Jia et al.131 described a twostep synthesis of trialkoxysilyl functionalized NHC precursor 105. In this work, the acetylated imidazolium salt 104 was first synthesized by direct quaternization of acetyl functionalized bromide with 1-methylimidazole, followed by amidation with 3triethoxysilylpropylamine under solvent free conditions at 150 °C for 2 h, affording 105 in quantitative yield. Additionally, Pleixats et al.40 reported on the synthesis of 106 from the hydroxyl functionalized imidazolinium salt 21 and (3isocyanatopropyl)triethoxysilane in the presence of SmI2 and 1,3-dimethyltetrahydropyrimid-2-one in anhydrous DMF solution at room temperature. Apart from the widely used quaternization approach, multistep syntheses starting with a cyclization reaction have been described for the preparation of the diaryl N-substituted NHC precursors 107−120 (Scheme 13 and Scheme 14). In order to synthesize the trialkoxysilyl functionalized imidazolium salts 112−113, the diarylhalide substituted NHC precursors 107−111 were prepared by the cyclization reaction between the respective diamine and cyclization reagents such as chloromethyl pivalate (CMP) or paraformaldehyde.132−137 Silver trifluoromethanesulfonate or tetrafluoroboronic acid were used to introduce different counterions to the desired products. The arylhalide functionalized NHC precursors 107−

imidazoles are usually not commercially available and thus need to be synthesized for further quaternization reactions. Therefore, this approach is reported less frequently, although it can be an effective method to obtain specially designed trialkoxysilyl functionalized NHC precursors. It should also be noted that the preparation of symmetric bis-functionalized imidazolium salts such as 86 is usually conducted in one-pot sequential substitutions of the two nitrogen atoms in the imidazole using two equiv of functionalized alkyl halides.120,121 The preparation of the trialkoxysilyl functionalized NHC precursors 94−99, 102−103, and 105−106 has been realized by multistep reactions starting with the direct quaternization of N-substituted imidazoles (Scheme 12). Iglesias and coworkers124−129 described a series of unsymmetrical trialkoxysilyl functionalized NHC precursors 94−99 and 102−103 for the immobilization of pincer-type gold and rhodium NHC complexes. The imidazolium salts 92−93 were initially prepared by direct quaternization of 2,6-bis(bromomethyl)pyridine with 0.67 equiv of the corresponding N-substituted imidazoles in acetone under reflux for 16−18 h.130 Addition of 93 to the respective N-alkyl-3-(trialkoxysilyl)propan-1-amine in the presence of a base finally yielded the trialkoxysilyl functionalized NHC precursors 94−96 in quantitative yields.111,128 Likewise, pyrrolidine derived trialkoxysilanes were also used with 92−93 to synthesize the trialkoxysilyl functionalized NHC precursors 97−99 in good yields (70− 75%).126,129 Later, the same group employed a similar synthetic strategy to prepare the dioxolane-modified asymmetrical and chiral NHC precursors 102−103, which were then used for the G


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Table 1. Direct Quaternization of (3-Halopropyl)trialkoxysilanes and N-Substituted Imidazoles for Preparation of Trialkoxysilyl Functionalized NHC Precursors 55−83

a

compd

R1

X

R2

solvent

T (°C)

reaction time (h)

yield (%)

55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83

Me Me Me n Bu n Bu n Bu n Bu t Bu Hexyl Decyl HDecyla Ph Mes Mes Mes Mes Mes Mesb DiPP DiPP DiPP DiPP Pyr TEG OPr Ph(Ac) Bn Cy C6Im

Br Cl Cl I Br Cl Cl I Cl Cl Cl Br I I Br Cl I Cl I I Br Cl(I) I Cl Cl I Cl I Cl

OMe OMe OEt OiPr OEt OMe OEt OMe OMe OEt OEt OMe OMe OEt OMe OEt OiPr OEt OMe OiPr OMe OEt OMe OEt OiPr OMe OEt OMe OEt

− toluene/− toluene/CH3CN/− CH3CN − toluene/− toluene/− 1,4-dixoane toluene toluene/THF toluene − 1,4-dixoane/− diglyme/CH3CN − − CH3CN − CH3CN CH3CN CH3CN DME toluene toluene CH3CN toluene − toluene toluene

60 80−110 70−100 reflux − 110−120 70−100 120 110 100−105 100 80 110−120 80−160 80 90 90 − 100 reflux 100 reflux reflux 110 reflux 100 − reflux 100

12 12−72 48−72 24 − 8−12 24−3 (days) 12 12 24 24 6 12 24 6 5 (days) 24 − 7 24 7 5 (days) 24 48 24 18 − 24 72

−78 58−9879−88 88−8989−95 9296 −97 70−9784,98,99 8094,100 96101 −84 7194,102 −94 79103 90−97101,104 90−99105−107 8678,103 8565,108,109 8996 −110 96103,111 8996 76103 85112 95111,113 89114 84115 77116 −117 95118 8291

Hexadecylimidazole. bImidazoline.

108 and 110 were then further silylated with triethoxysilane in the presence of a Rh catalyst and trimethylamine to finally afford the trialkoxysilyl functionalized NHC precursors 112− 113 in good yields (50−80%).132−134 Moreover, the alkenyl functionalized imidazolium salts 43 and 48−52, which were prepared by cyclization, can be further transformed into the trialkoxysilyl functionalized compounds 114−119 (Scheme 14). The syntheses of 114−116 were accomplished by hydrosilylation of 48−49 and 53, with trichlorosilane in the presence of a Pt catalyst,63−65 while the preparation of 117− 119 (82−93%) was carried out by attaching 3-mercaptopropyl(triethoxy)silane to the alkenyl groups of 50−52 using a photoor AIBN-initiated thiol-ene reaction.66−68 Additionally, Buchmeiser et al.37 reported the synthesis of the trialkoxysilyl functionalized NHC precursor 120 by a Mo-catalyzed polymerization of the norbornene functionalized monomer 43. In this work, the trialkoxysilyl group was introduced by endcapping the polymerization reaction with excess amount of ω(trialkoxysilyl)propyl isocyanate in CH2Cl2 at ambient temperature. 2.1.4. Carboxyl Functionalized NHC Compounds. Carboxyl groups possess a versatile reactivity as they may be further transformed into carboxylate salts, esters, amides, acid chlorides, and alcohols. Thus, the preparation of carboxyl

functionalized NHC ligands can be an attractive choice in order to immobilize NHC compounds. Niu et al.138 reported the use of 2-chloroacetic acid for the direct quaternization of 1methylimidazole in toluene under reflux conditions for 24 h. The resulting carboxyl functionalized imidazolium salt 121 can further react with thionyl chloride to produce the acyl chloride bearing NHC precursor 122 (Scheme 15). Furthermore, the quaternization of carboxyl functionalized imidazoles by alkyl halides was also described. However, due to the comparatively high reactivity and acidity of the carboxyl group, the protection of this group is usually required during the synthesis of the imidazolium salts. Hence, an additional deprotection step is essential to eventually obtain the carboxyl functionalized NHC precursors by this approach. 123−127, for example, were obtained by direct quaternization of an imidazole bearing a protected carboxylic acid functionality (Scheme 16).139−142 The quaternization step in the syntheses of 123− 124 required only 10−25 min as it was carried out in DMF at 110−150 °C using microwave irradiation, while the same step for the synthesis of 125−126 took 4 days in toluene under refluxing conditions. Yaghi and co-workers142 reported the quaternization of an imidazole structure containing a diesterterminated linear terphenyl backbone, with methyl iodide for the synthesis of a diester-terminated imidazolium salt. Further H


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following deprotection of the ester group afforded the dicarboxyl functionalized NHC precursor 133 in 92% yield. 2.1.5. Alkynyl Functionalized NHC Compounds. Alkynyl groups can readily react with azides to form a triazole ring under mild conditions (known from click chemistry) and have proven their suitability for immobilization purposes.145,146 By direct quaternization of alkyl bromide substituted alkynes with various imidazoles, the alkyne functionalized imidazolium salts 134−139 can be easily prepared in good to excellent yields (Scheme 18).147−153 In general, these reactions proceed in solution at 80−110 °C for 12−24 h. The amphihilic bisimidazolium salt 134 was prepared from a di(bromomethyl) substituted arene by reaction with an imidazole bearing a long alkyl chain.153 It was subsequently used for the stabilization of gold nanoparticles. The synthesis of 138 was conducted in THF in a sealed tube; therefore an elevated reaction temperature of 90 °C could be applied.150 Furthermore, 136 was synthesized in different yields (32 and 99%) depending on the reaction conditions.147,151 2.1.6. Amine Functionalized NHC Compounds. Due to their basicity and nucleophilicity, amine groups can easily undergo alkylation, acylation, sulfonation, and condensation reactions to form amines, imines, or ammonium ions. In view of this, the synthesis of amine-group-bearing NHC ligands is also an applicable choice for the immobilization of NHC compounds. The synthesis of amine functionalized NHC precursor 140 by refluxing 2-bromopropylamine hydrobromide and 1-methylimidazole was reported by several groups (Scheme 19).154−156 In this synthesis, the hydrohalide salts of the amine substituted alkyl halides rather than the alkyl halides themselves were used to directly quaternize the N-substituted imidazole in order to prevent an undesired internal cyclization reaction. Furthermore, Skowerski et al.157−159 prepared the amine bearing imidazolinium salts 141 and 142 in order to further synthesize ammonium tagged NHC compounds, which can be immobilized via the strong interaction of the ammonium group with surface-bound silanol functionalities. In order to synthesize 141−142, the ammonium tagged bis-imines were initially prepared followed by cyclization with triethylorthoformate in the presence of (NH4)BF4, providing the desired products in high yields (78−83%). 2.1.7. Multitopic NHC Compounds. Multitopic, especially bidirectional, ditopic organic ligands are widely reported for the preparation of main-chain organometallic polymers (MCOPs), which have great potential for a broad range of applications as recyclable solid catalysts.160 A series of facially opposed ditopic NHC precursors 143−153 for NHC based MCOPs was synthesized by quaternization of the corresponding ditopic imidazole structures with alkyl halides in the presence of NaH (Scheme 20).161−166 Furthermore, the phenol bearing ditopic NHC precursor 154 was prepared in 93% yield by direct quaternization of the respective benzobis(imidazole) compound with 1-bromobutane in DMF solution (Scheme 21).167 Apart from the ditopic NHC compounds, Zhang et al.168 prepared the tripodal imidazolium salt 155, which was based on a triptycene structure, by methylation of the triptycene based imidazole compound with methyl iodide in DCM at room temperature for 48 h. Ditopic NHC precursor 156 on the other hand was synthesized using a cyclization approach (Scheme 22).169 Therein, the presynthesized diamine was cyclized with triethylorthoformate in the presence of (NH4)BF4 in toluene solution, providing the desired product in 78% yield. However, the key synthetic steps for these specially

Scheme 11. Preparation of Trialkoxysilyl Functionalized NHC Precursors 84−91 by Direct Quaternization of Trialkoxysilyl Functionalized Imidazoles and Imidazolines93,107,119−123

deprotection of the synthesized diester with HBF4·OEt2 eventually afforded the desired dicarboxyl functionalized NHC precursor 127 in quantitative yield. Additionally, the cyclization route has been employed for the synthesis of dicarboxyl functionalized imidazolium salts 128 and 131−133 (Scheme 17). 128 was directly prepared by the cyclization of the respective dicarboxyl functionalized diamine with paraformaldehyde, while the syntheses of 131 and 132 were accomplished by two synthetic steps. The cyano imidazolium salts 129 and 130 were initially prepared by cyclization of cyano diamines with paraformaldehyde. Refluxing 129 and 130 in HBr or HCl transformed them into the desired dicarboxyl functionalized imidazolium salts 131 and 132.143,144 133 was prepared from the aryl chloride functionalized imidazolium salt 109, which was reacted with CO and MeOH in the presence of a Pd catalyst in an autoclave to produce the ester-protected imidazolium compound.137 The I


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Scheme 12. Multistep Syntheses of the Imidazolium NHC Precursors 94−99, 102−103, and 105−106 with Trialkoxysilyl Functionalities40,111,124−131

designed NHC precursors (143−154) are usually not the final quaternization or cyclization step but the preparation of the corresponding diimine, diamine, or imidazole structures. 2.1.8. Soluble Polymer Functionalized NHC Compounds. Soluble polymers have been used as supports for the synthesis and immobilization catalysts as they can serve as a phase anchor.170−172 Therefore, the recovery of the soluble polymer-bound catalysts is facilitated (biphasic catalysis or recovery by solvent precipitation). Moreover, they have certain advantages regarding characterization compared to solid supports and their reactivity is very predictable. In this sense, the preparation of soluble polymer functionalized NHC precursors is of considerable synthetic value in order to realize the immobilization of NHC compounds. The use of halideterminated polymers (or other leaving groups) to directly quaternize N-substituted imidazoles has been reported to prepare the soluble polymer functionalized imidazolium salts 157−163 in a single step (Scheme 23).173−177 In these syntheses, the two reactants were simply mixed together or dissolved (e.g., toluene, DMSO) and heated to the respective reaction temperatures for 12−24 h. With respect to the syntheses of 161 and 162, LiCl or NaCl was also added to the

reaction mixture to induce an anion exchange.173,176 The preparation of the polyTHF-supported NHC precursor 163 was accomplished by a one-pot sequential reaction.175 In this synthesis, the triflate-terminated polyTHF compound was initially prepared by cationic ring opening polymerization of tetrahydrofuran for further quaternization with 1-ethylimidazole, affording the desired NHC precursors in 36−40% yields. Furthermore, Shi et al.178 prepared the PEG-tethered NHC precursors 164 and 165 by quaternization of PEG-substituted imidazoles with ferrocenyl acetate in the presence of NaI in acetonitrile at 50 °C for 48 h (Scheme 24). A series of soluble polymer-bound NHC precursors 166−169 was synthesized by cyclization of polyethylene (PE) or polyisobutylene (PIB) bound diamines (diimines) with the corresponding ring-closing reagent (e.g., triethylorthoformate, chloromethyl ethyl ether) (Scheme 25).176,179−181 Depending on the ring-closing agent and additives, different counterions were received. In addition to these direct syntheses starting from soluble polymer precursors, the covalent binding of the imidazolium salts with suitably functionalized, soluble polymers is also a practical choice to obtain soluble polymer functionalized NHC precursors. The alkynyl functionalized NHC precursors 136, J


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Scheme 13. Multistep Synthesis of Trialkoxysilyl Functionalized NHC Precursors 112−113 from Arylhalide Functionalized Imidazolium Salts 107−111132−137

Scheme 14. Preparation of the Trialkoxysilyl Functionalized NHC Precursors 114−120 from Alkenyl Functionalized NHC Precursors 43 and 48−5337,63−68

137, and 139 were reported to react with polymer-bound azide compounds via click chemistry to afford the soluble polymeric NHC precursors 170−174 (Scheme 26).147,150,152,181 However, 173 and 174 were obtained in relatively low yields (17− 45%), which may be attributed to the high steric demand of the polymers used, as claimed by the authors.152 Meanwhile, the other two precursor types, 170−171 and 172, were synthesized in high yields (80−99%),147,181 which was a reasonable result considering the highly efficient click reactions employed. Furthermore, Wang and co-workers25 reported the use of PEG-bound succinic acid to synthesize the PEG supported NHC precursor 175 by esterification with 2 in the presence of an additional dehydrating agent DCC (N,N′-dicyclohexylcarbodiimide) and a catalytic amount of DMAP (4-dimethylaminopyridine).25 2.1.9. NHC Compounds Bearing Miscellaneous Functional Groups. Apart from those functionalities mentioned above, some other, more uncommon functional groups have also been incorporated into NHC precursors via both direct quaternization and cyclization methods for the purpose of immobilization. Weberskirch et al.182−184 and Lee et al.185 reported the preparation of bromo functionalized imidazolium salts 176−179. In order to obtain the monosubstituted compounds, 1-methylimidazole was added to an excess amount of dibromoalkane in solution (DMF or DCM) before heating to the desired temperature (Scheme 27). In a second step 179 could be further converted into thiol functionalized imidazolium salt 180 by using potassium thioacetate as the source of nucleophilic sulfur.185 The thiol moiety was subsequently used as an anchoring site to create self-assembled monolayers of 180 on a gold surface (section 2.2.5.4). Mata et al.186 described the synthesis of the formyl functionalized NHC precursor 181 by stirring a mixture of 4-(chloromethyl)benzaldehyde and 1methylimidazole in THF solution at 60 °C for 72 h (Scheme

Scheme 15. Preparation of the Carboxyl Functionalized NHC Precursors 121−122 by Direct Quaternization of 2Chloroacetic Acid and 1-Methylimidazole138

28). Via a condensation reaction the corresponding Ir complex could be immobilized on imine functionalized magnetic nanoparticles (section 2.2.2.3). The phosphonate functionalized NHC precursors 182−183 were prepared by quaternization of 4-bromobutyl phosphonate ester with the corresponding aryl-substituted imidazoles in dioxane or toluene at 80 °C for 8−10 h (Scheme 29).187 It should be noted that both compounds were not isolated in pure form but in a mixture with unreacted 4-bromobutyl phosphonate ester. Yet, they were successfully applied in the heterogenization via a sol−gel K


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Scheme 16. Syntheses of the Carboxyl Functionalized NHC Precursors 123−127 by Direct Quaternization of Carboxyl Functionalized Imidazoles139−142

Scheme 17. Preparation of the Dicarboxyl Functionalized NHC Precursors 128 and 131−133 by Cyclization137,143,144

Scheme 18. Preparation of Alkynyl Functionalized Imidazolium Salts 134−139147−153

approach. In order to use the catch−release concept for immobilization (thermodynamically controlled π-stacking), Reiser et al.188 and Peris et al.189,190 described pyrene bearing NHC precursors 184 and 185, which were synthesized in a one-step quaternization of 1-methyimidazole with 1(bromoalkyl)pyrene (Scheme 30). The fluoride functionalized NHC precursor 186 was prepared by a one-pot sequential substitution of the imidazole with 3 equiv of perfluorodecyl iodide in toluene at 110 °C for 24 h (Scheme 31).191 The functional group plays a central role in the immobilization of the corresponding Pd−NHC complex via weak fluorophilic interactions (section 2.2.5.4). Quaternization of 1-methyimidazole with 1,3-propane sultone in acetonitrile solution under reflux conditions yielded the sulfonated imidazolium salt 187 (Scheme 32).192,193 The introduction of a charged functional group opens the door toward immobilization strategies relying on electrostatic interaction and an altered solubility. In order to obtain a suitable monomer for electrochemical polymerization, Cowley and co-workers194,195 synthesized the bis(bithiophene) substituted NHC precursor 188 in 87% yield by cyclization of the corresponding bis(bithiophene) substituted diimine with paraformaldehyde in the presence of HCl (Scheme 33). The cyclization of an anthracene-tagged diamine with triethyl orthoformate in the presence of KBF4 yielded anthracene functionalized imidazolinium salt 189 in 62% yield (Scheme 34).196 The latter was subsequently metalated with a Ru

precursor and immobilized on silica particles via charge-transfer interactions (section 2.2.5.4). Considering the two basic synthetic routes for generating the NHC precursors, i.e. quaternization and cyclization, it is clear that quaternization is the predominantly used method. It allows easy synthetic access following a straightforward procedure using mild reaction conditions. Most functional groups that are of relevance can be introduced using the quaternization route, and synthetic interferences with side groups are minimal. However, the cyclization approach can also be advantageous L


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Scheme 19. Preparation of Amine Functionalized NHC Precursors 140−142 by Quaternization and Cyclization Methods154−159

Scheme 22. Synthesis of Ditopic NHC Precursor 156 by Cyclization169

Scheme 23. Preparation of Polymer Functionalized NHC Precursors 157−163173−177 Scheme 20. Preparation of the Ditopic NHC Precursors 143−153 by Direct Quaternization of Facially Opposed Bisimidazoles with Alkyl Halides161−166

Scheme 21. Multitopic NHC Precursors 154 and 155 Synthesized by Direct Quaternization167,168

symmetrically substituted NHC precursors, the cyclization approach is definitely the method of choice. Still, certain precautionary measures have to be taken depending on the reaction conditions, e.g. the protection of other functionalities such as alcohols or carboxyl groups. 2.2. Heterogenization of NHC Compounds

since it allows high flexibility and many suitable amines and imines are commercially available. Moreover, when synthesizing

Discussing the heterogenization of NHC compounds, typically three aspects are of importance: first the immobilization M


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Scheme 24. Preparation of Polymer Functionalized Imidazolium Salts 164 and 165 by Direct Quaternization of PEG-Substituted Imidazoles with Ferrocenyl Acetate178

Scheme 27. Synthesis of Bromo and Thiol Functionalized NHC Precursors 176−180182−185

Scheme 28. Synthesis of Formyl Functionalized NHC Precursor 181186

Scheme 25. Preparation of the Soluble Polymer Functionalized NHC Precursors 166−169 via Cyclization of the Corresponding Polymer-Bound Diamines or Diimines176,179−181

Scheme 29. Synthesis of Phosphonate Functionalized NHC Precursors 182−183187

Scheme 30. Synthesis of Pyrene Functionalized NHC Precursors 184−185188−190

Scheme 26. Synthesis of Soluble Polymer Functionalized Imidazolium Salts 170−17525,147,150,152,181

Scheme 31. Synthesis of Fluoride Functionalized NHC Precursor 186191

method, second the immobilization position, and third the supporting material (Figure 4). Among the various immobilization methods, solid synthesis, covalent grafting, and selfsupport are the three predominant ones for NHC compounds, N


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via the benzylidene ligand of, e.g., a Grubbs II complex. However, the applied immobilization strategy may have significant consequences for the recyclability of the catalyst as the benzylidene ligand decoordinates from the ruthenium center during the catalytic metathesis reaction. This issue is further discussed in section 4.3. With respect to the supporting materials, organic polymers and silica-based materials are the two most widely employed solid supports for NHC compounds. Besides, carbon-based materials (i.e., carbon nanotubes, graphene oxide), metal NPs as well as coordination polymers are also used as supports in a certain number of examples. In order to elucidate criteria for the selection of supporting materials, NHC compounds will be grouped according to their support within each section. 2.2.1. Solid Phase Synthesis. In the context of heterogenization solid phase synthesis refers to a process in which the formation of the NHC moiety or precursor is conducted directly on the solid support by a quaternization or cyclization approach. Since NHC precursors can be prepared by a single step quaternization of N-substituted imidazoles with alkyl halides in good to excellent yields, the use of solidified alkyl halides is a simple and practicable option. Solid materials bearing benzyl chloride functionalities on their surface are frequently reported for the direct quaternization of Nsubstituted imidazoles on support (Table 2). Merrifield polystyrene resins, which can be readily prepared or purchased from commercial suppliers,198 were used to prepare a series of PS-supported NHC precursors 190−201 in a single step. In most of the syntheses, the Merrifield resins reacted directly with an excess amount of N-substituted imidazoles in aprotic solvents (e.g., toluene) at 80−110 °C for 12−48 h, providing the corresponding PS-supported compound in quantitative yields. However, Luis et al.199,200 reported the synthesis of 195 in neat 1-methylimidazole without using additional solvent in much shorter reaction times of 0.5−3 h. For 190−201 imidazolium loadings between 0.21 and 3.02 mmol/g were obtained. It should be noted that the final NHC loadings are mainly determined by the amount of benzyl chloride groups in the original Merrifield resin rather than the reaction conditions (e.g., solvent, time). Besides, imidazoles can be incorporated due to swelling of the polymer during long reaction times without being bound covalently, which can influence the exact loading. For other N-substituted imidazoles, especially those bearing bulky substituents (mesityl or 2,6-diisopropylphenyl), lower reaction efficiencies were observed as revealed by the loadings of 197, 198, and 200 (Table 2). Besides pure polymer resins, the use of polystyrene-coated magnetic nanoparticles (MNPs) bearing benzyl chloride functionalities was reported by Lin et al.201 for the synthesis of supported NHC precursor 202 by direct quaternization. Albeit Merrifield PS resins are mainly used for the direct quaternization of N-substituted imidazoles in a single step, multistep syntheses were also reported for the preparation of the PS-supported NHC precursors 203−209 (Scheme 35). Chi and co-workers222 reported the use of PS-supported linear alkyl chloride, which was prepared by substitution of the chlorobenzyl group of a Merrifield resin by 6-chloro-1-hexanol. By reaction with 1-methylimidazole at 90 °C for 3 days, imidazolium salt 203 was obtained with a loading of 2.5 mmol/g. Luis et al.199,214,216 reported the formation of PS-supported imidazolium salts 204−208 by three different synthetic approaches starting from a commercially available Merrifield resin. 204 and 205 carry additional ionic liquid

Scheme 32. Synthesis of Sulfonated NHC Precursor 187192,193

Scheme 33. Synthesis of Bis(bithiophene) Functionalized NHC Precursor 188194,195

Scheme 34. Synthesis of Anthracene Functionalized NHC Precursor 189 by Cyclization196

Figure 4. Main aspects regarding the heterogenization of NHC compounds.

while other methods such as absorption, entrapment, electrostatic interaction, and π−π stacking are less frequently reported, and therefore are summarized under miscellaneous methods (section 2.2.5) Recently, a growing interest in binding NHCs to metal surfaces such as metal NPs has emerged.197 The immobilization position is usually predetermined by the functionalities introduced during the formation of the NHC moiety (section 2.1); thus this aspect will not be discussed in detail in this section. It is worth mentioning that the immobilization via the metal (Figure 4, position c) is often used in the preparation of NHC-stabilized metal NPs as well as the immobilization of Ru−NHC complexes used as metathesis catalysts. In the latter case immobilization is frequently realized O


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Table 2. Preparation of PS-Supported Imidazolium NHC Precursors 190−202 via Direct Quaternization of Benzyl Chloride Modified Materials with N-Substituted Imidazoles

a

compd

R

solvent

T (°C)

reaction time (h)

loading (mmol/g)

supporting material

190 191 192 193 194 195 196 197 198 199 200 201 202

Me Me Me Me Me Me Bn Mes Mes Mes DiPP Fema DiPP

CHCl3 NMP DMF toluene toluene − toluene NMP DMF/THF CHCl3 toluene DMF toluene

50 80 80 80 110 90 80 80 70 60 90 60 90

24 12 24 24 24 0.5−3 24 48 48 48 24 72 24

− 1.91 0.95 2.74 2.95 0.39−3.02 0.92 0.61 0.32 0.34 0.21 1.41 0.21

PS202 PS203−209 PS210 PS211 PS212 PS199,200,213−216 PS217 PS218 PS219 PS220 PS201 PS221 PS-MNPs201

1-N-Ferrocenylmethyl benzimidazole.

Scheme 35. Multistep Syntheses of the PS-Supported NHC Precursors 203−209 with Merrifield PS Resin as the Starting Material199,214,216,222,223

P


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quaternization of N-substituted imidazoles with chlorobenzyl functionalized silica material, which was synthesized by the reaction of trichloro-4-(chloromethyl)phenyl silane with activated SiO2. In these studies, the silica material reacted with N-substituted imidazoles in toluene solution at 70−80 °C for 24 h, affording the desired silica-supported NHC compounds with high loadings ranging from 0.81 to 1.10 mmol/g (close to the theoretical value of 1.12 mmol/g). Thieuleux and co-workers230−235 described the preparation of 218 and 219 using chlorobenzyl functionalized mesoporous silica material, which was synthesized by co-condensation of p(chloromethyl)phenyltrimethoxysilane and tetraethoxysilane (TEOS) in the presence of Pluronic P-123 as a template under acidic conditions. With this chlorobenzyl functionalized silica material, 218 was obtained by direct quaternization of 1methylimidazole at 135 °C for 20 h, while the preparation of 219 was conducted by refluxing of the silica material with an excess amount of mesitylimidazole in toluene for 48 h. Using the same strategy as for the synthesis of 218 and 219 a mesoporous-silica supported alkyl iodide was synthesized and further reacted with an excess amount of mesitylimidazole in toluene under reflux conditions for 48 h, yielding the mesoporous silica supported NHC precursor 220 (Scheme 37).231

functionalities and were prepared by the treatment of presynthesized PS-supported imidazoles with terminal dibromoalkanes followed by the quaternization with tributylamine or pyridine, respectively.216 204−206 were synthesized by direct quaternization of 1-methylimidazole with the corresponding PS-supported dichloride compounds. In this context the authors observed that the amount of the chloromethylene groups on the PS resin can be controlled by addition of diethanolamine during the first reaction step. This allows the synthesis of PS-supported imidazolium salt 208 bearing two different imidazolium fragments.216 Furthermore, Blechert and co-workers223 described the solid synthesis of PS-supported NHC precursor 209 by attaching a hydroxyl functionalized diamine to the Merrifield PS resin followed by cyclization with triethylorthoformate. The xanthine derived imidazolium salts 210 and 211 were obtained by reaction of theophylline and caffeine with a Merrifield resin (Scheme 36).224 In the case of Scheme 36. Synthesis of Xanthine Derived Imidazolium Salts 210 and 211224

Scheme 37. Synthesis of Silica-Supported NHC Precursor 220 by Direct Quaternization231

caffeine, bearing an additional methyl group, a single reaction step was sufficient to form the corresponding imidazolium salt, whereas for theophylline the subsequent quaternization with ethyl iodide was required. However, a significantly higher coupling efficiency was observed for the latter case. Besides polystyrene, benzyl chloride functionalized silica materials were also employed for the preparation of silicasupported imidazolium salts (Table 3). Wang et al.,225−229 for example, described the preparation of 212−217 by direct

Despite the higher synthetic complexity of solid-supported imidazoles compared to alkyl halides, the synthesis of immobilized NHC compounds by direct quaternization of supported imidazoles with free alkyl halides has also been reported (Scheme 38). Moreau et al.236 described an imidazolecontaining silica hybrid material prepared by a sol−gel synthesis of 3-(triethoxysilyl)propyl imidazole and TEOS in the presence of a template reagent (cetylpyridinium chloride). This silica

Table 3. Preparation of Silica Supported Imidazolium NHC Precursors 212−219 via Direct Quaternization of Benzyl Chloride Modified Materials with N-Substituted Imidazoles

a

compd

R

solvent

T (°C)

reaction time (h)

loading (mmol/g)

supporting material

212 213 214 215 216 217 218 219

Me t Bu Ph Bn Pyrra Mes Me Mes

toluene toluene toluene toluene toluene toluene − toluene

80 80 80 80 70 80 130 110

24 24 24 24 24 24 20 48

0.96 0.92 0.87−0.95 0.81−0.97 0.92 0.96−1.10 0.50 0.33

silica225,226 silica225 silica225 silica225 silica229 silica227,228 silica232 silica230−235

tert-Butyl (S)-2-((1H-imidazol-1-yl)methyl)pyrrolidine-1-carboxylate. Q


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Scheme 38. Preparation of Supported NHC Precursors by Direct Quaternization of Supported Imidazoles with Alkyl Halides

Scheme 40. Preparation of Silica Supported NHC Precursor 228 by Free Radical Polymerization239

material was quaternized with four different alkyl halides to prepare the silica-supported NHC precursors 221−224, respectively (Scheme 39). Similarly, Thieuleux and co-workers234,237 prepared an imidazole containing silica hybrid material by using different imidazole−triethoxysilane precursors and a template reagent (P-123). The obtained silica material was then reacted with benzyl chloride in toluene under reflux for 24 h to afford 225. By grafting of imidazolinyl functionalized triethoxysilane onto silica coated MNPs, Lee et al.238 prepared imidazoline containing MNPs, which afforded supported NHC precursors 226 and 227 upon reaction with 2-picolyl chloride or benzyl chloride at 80 °C in chloroform for 12 h. The imidazolium loadings of 226 and 227 were found to be 0.46 and 0.67 mmol/g, respectively. Tamami and co-workers239 reported the synthesis of a silicasupported imidazole precursor by a free radical polymerization reaction between vinylimidazole and acrylamidopropyl functionalized silica (Scheme 40). The silica-supported precursor was subsequently treated with methyl iodide in DMF and NaCl in order to synthesize the silica-supported NHC precursor 228, with a loading of 1.3 mmol/g. Furthermore, Moghadam et al.240,241 described the preparation of Si-NP supported NHC compound 229 (loading 0.32 mmol/g) by methylation of silicaNP supported bis(imidazoles) with methyl iodide in THF at 80 °C for 24 h (Scheme 41). In addition to polystyrene- and silica-based supporting materials, other materials carrying alkyl halide functionalities have been used in the synthesis of supported imidazolium salts via direct quaternization of N-substituted imidazoles. Wright et al.187 prepared a bromobutyl functionalized zirconium phosphonate (ZrP) support by acid hydrolysis of 4-bromobutyl phosphonate ester followed by hydrothermal reaction with ZrOCl2. The derived ZrP-supported NHC compound was synthesized by mixing of the ZrP material with 1methylimidazole in 1,4-dioxane under refluxing conditions for 2 days. It should be noted that the bromobutyl functionalized

Scheme 41. Preparation of Silica Supported NHC Precursor 229240

zirconium phosphonate material was only suitable for the immobilization of sterically unhindered imidazole substrates. Glorius et al.242 reported the functionalization of MNPs with (3-chloropropyl)triethoxysilane for further preparation of MNP-supported imidazolium salt 230 (Scheme 42) The chloropropyl functionalized MNPs were reacted with an enantiomerically pure (R)-BINOL-derived imidazole in toluene under reflux for 16 h, affording 230 with an NHC loading of 0.23 mmol/g. Another MNP-supported NHC ligand was synthesized by reaction of chloropropyl functionalized MNPs and 1-methylimidazole in toluene at 90 °C for 24 h.243 In contrast to the

Scheme 39. Synthesis of Immobilized NHC Precursors 221−227 by Direct Quaternization of Silica-Supported Imidazoles234,236−238

R


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Scheme 42. Synthesis of MNP-Supported NHC Precursor 230 by Direct Quaternization242

Scheme 44. Synthesis of Polymer-Supported NHC Precursor 234 by Direct Quaternization245

Scheme 45. Preparation of Imidazolium Functionalized PAFs as NHC Precursors 235 and 236246

synthesis of 230, in this case the supporting material was prepared by coating mesoporous silica onto Fe3O4−NPs followed by the reaction with (3-chloropropyl)trimethoxysilane. Albéniz et al.244 prepared an alkyl bromide functionalized polynorbornene support by a Ni-catalyzed copolymerization of norbornene and bromobutylnorbornene for the preparation of 231−233 (Scheme 43). In this work, the

Ir and Ru precursors generating the corresponding immobilized NHC complexes, which were highly active catalysts for transfer hydrogenation and the N-alkylation of amines with alcohols. Furthermore, imidazole functionalized carbon materials were employed for the preparation of the supported imidazolium salts 237−239 (Scheme 46). Lee and co-workers247 first

Scheme 43. Synthesis of Polymer-Supported Imidazolium Salts 231−233 by Direct Quaternization244

Scheme 46. Preparation of Carbon Supported NHC Precursors 237−239247−249

synthesized a multiwalled carbon nanotube (MWCNT) supported imidazole precursor by the treatment of acyl chloride functionalized MWCNTs with an excess amount of 3aminopropylimidazole. The imidazole functionalized MWCNTs were then reacted with neat bromobutane at 80 °C for 24 h to yield the desired MWCNT-supported NHC precursor 237. A similar strategy was employed by Serp et al.248 and Karousis et al.249 to prepare the carbon nanotube (CNT) supported NHC precursor 238 and the graphene oxide supported NHC precursor 239. A slightly different approach was used to obtain immobilized imidazolium salt 240, comprising the direct quaternization of methylimidazole by an acyl chloride functionalized CNT support (Scheme 47).250

alkyl bromide functionalized polynorbornene reacted with 1methylimidazole in toluene under reflux conditions for 60 h, while for the reaction with bulky mesityl- and 2,6diisopropylphenylimidazoles, the syntheses were conducted under microwave irradiation at 170 °C for 50 min. Wu et al.245 reported the synthesis of the mesopolymer (FDU-15 type) supported NHC precursor 234 by the direct quaternization of 1-methylimidazole with a chloromethylated mesopolymer in toluene at 80 °C for 24 h (Scheme 44). The benzyl chloride functionality of the mesopolymer was introduced by chloromethylation of the phenyl ring present in the structure with AlCl3 and chloromethyl methyl ether. In a recent publication, chloro substituted polymeric aromatic frameworks (PAFs) have been successfully functionalized with imidazolium moieties via the quaternization route (Scheme 45).246 The obtained solid NHC precursors (235 and 236) were successfully reacted with

Scheme 47. Synthesis of CNT Supported NHC Precursor 240250

S


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synthesis of NHC precursors, the most prominent supports are Merrifield resins and silica, since these are inexpensive, commercially available materials, which still offer a high flexibility. While Merrifield resins are already offering a halide functionality for direct quaternization, silica particles require a primary substitution. However, they offer higher flexibility for more versatile starting points. Beside these two major players, many different materials such as polymers, CNTs, and MNPs can be used for solid phase synthesis if functionalized properly at the cost of a higher synthetic effort. 2.2.2. Covalent Grafting. Grafting of ligand precursors or metal complexes to a solid support via a covalent bond is by far the most frequently employed strategy for the immobilization of homogeneous catalysts. This method does not only provide the strongest binding between support and catalytically active species but also allows diversified synthetic routes. Since NHC ligands exhibit high flexibility regarding the introduction of functional groups, this grafting method is widely used for the immobilization of NHC compounds as well. In a typical grafting process, the functionalized NHC compound reacts with a surface-modified material according to a well-established organic reaction between their functional groups. In this sense, sections 2.2.2.1 and 2.2.2.2 will summarize examples of covalent grafting of NHC compounds according to the functional groups and supporting materials employed. 2.2.2.1. Grafting of Hydroxyl Functionalized NHC Moieties. Hydroxyl groups exhibit high synthetic flexibility and are able to undergo several different types of reactions (e.g., acetylation, nucleophilic substitution, and reduction) with acids, bases, and nucleophilic agents. Therefore, grafting of hydroxyl functionalized NHC precursors or complexes to solid supports is a practicable immobilization approach that has been reported for many cases. Generally, the formation of ether and ester bonds by nucleophilic substitution or acetylation is the most typical binding model applied for this purpose. The first supported NHC−Pd complexes (246 and 247) were prepared by Hermann et al.33 by grafting the hydroxyl functionalized bis-NHC−Pd complexes 244 and 245 onto a commercially available PS resin (Wang resin, 2.7 mmol of Br/g, Scheme 50). The substitution of bromide by hydroxyl groups of complexes 244 and 245 in the presence of a bulky organic base (diisopropylethylamine) at room temperature afforded the immobilized bis-NHC−Pd complexes 246 and 247 with an ether linkage. The Pd loading of 246 and 247 was found to be 1.0 and 1.1%, respectively, as determined by elemental analysis. The same synthetic approach was used by Kühn and coworkers (Scheme 50).34 Reaction between NHC−Pd complex 248 and a bromomethyl functionalized PS resin (Wang resin, 1.9 mmol Br/g) afforded the immobilized complex 249 with a loading of 1.1% Pd. Similarly, Buchmeiser et al.39 described the synthesis of PSsupported NHC−Pd complexes 254 and 255 by grafting of the hydroxyl functionalized bis-NHC−Pd complex 253 to Merrifield and Wang resin (Scheme 51). Further, Luo et al.256 immobilized the bis-NHC compound 250 via an ether bond to a Merrifield PS resin (2.7 mmol of Cl/g) in the presence of tributylamine as the base (Scheme 50). However, due to the decreased reactivity of the chloromethyl compared to the bromomethyl group of the PS resin, the reaction required a longer reaction time (4 days at room temperature). Recently, by adopting this method, Salunkhe and co-workers257 synthesized PS-supported imidazolium salt 252 based on two slightly different chloromethyl functionalized PS resins (one

Differently functionalized supporting materials have also been employed in multistep syntheses to prepare immobilized NHC precursors. Wilczewska et al.251 used amine-terminated MNPs to prepare 241 (Scheme 48) by treatment with triethyl Scheme 48. Multistep Syntheses of the Supported NHC Precursors 241−242251−253

orthoformate and 2,6-dimethylaniline to afford a supported formamidinium compound, which was alkylated with 1,2dichloroethane. Trapp et al.252,253 reported the immobilization of the unusual NHC precursor 2-(pentafluorophenyl)imidazolidine (Scheme 48). During the multistep synthesis hydridomethyldimethyl polysiloxane (10.2% Si−H groups) was reacted with an alkene functionalized diamine in the presence of a Pt catalyst followed by the reaction with pentafluorobenzaldehyde under acidic conditions to afford the polysiloxane-supported NHC precursor 242. It should be noted that 242 can also be coated into fused-silica capillaries via initial attachment of the polysiloxane-supported diamine. More recently, a multicomponent cyclization reaction of amine functionalized MWCNTs, aniline, glyoxal, and formaldehyde was reported affording 243 in a single step (Scheme 49).254 Additionally, Meldal and co-workers reported the synthesis of PEGA-supported bis-NHC compound by solid-phase peptide coupling techniques.255 Although solid phase synthesis allows easy separation of the solid-bound products from the reaction mixture, it should be noted that characterization of the solid reaction products can pose difficulties and the presence of incompletely formed ligand molecules cannot be excluded. Considering the solid phase Scheme 49. Multicomponent Cyclization Reaction Affording 243254

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catalysts 259 and 260 by grafting the hydroxyl functionalized Grubbs I type NHC−Ru catalyst 258 onto chlorosilane functionalized silica gel (230−400 mesh, Scheme 53). The

Scheme 50. Immobilization of NHC Compounds via the Formation of Ether Bonds33,34,256

Scheme 53. Synthesis of the Grafted NHC−Ru Complexes 259 and 26029

latter was obtained by treatment of commercial silica gel with chlorosilanes in CH2Cl2 for 30 min. In this study, NHC complex 258 was prepared from 5 and reacted with the functionalized silica gel in CH2Cl2 for 5 min. However, a detailed evaluation and characterization of this immobilization process was not given in this case. Generally, the number of recent examples where grafting was realized through the formation of an ether bond is small since the coupling efficiency is comparatively low revealed by the long reaction times. Moreover, it usually requires an additional base, which may lead to the decomposition of the NHC precursor or the catalyst as mentioned above. Furthermore, covalent grafting of hydroxyl functionalized NHC compounds is often realized by the formation of an ester bond. Since the reaction between hydroxyl groups and acyl chlorides is a very efficient way to prepare ester bonds under mild reaction conditions (no or weak base), acyl chloride functionalized solid materials are frequently used for grafting purposes. Buchmeiser and co-workers 258 described the immobilization of hydroxyl functionalized NHC−Ru complex 258 by reaction with an acetyl chloride functionalized polynorbornene monolithic support, which was prepared by a graft-polymerization process, where a CH2Cl2 solution of norborn-5-ene-2-carboxylic chloride was passed over a polymer monolith-filled column at 45 °C for 15 h (Scheme 54). The

Scheme 51. Immobilization of Pd-NHC Complex 253 via the Formation of Ether Bonds39

Scheme 54. Immobilization of NHC Compounds via Ester Bond Formation35,258

containing an extra linking spacer), using a strong base (NaH) rather than the weak organic base tributylamine. Moreover, Lee et al.31 also reported the use of tBuOK as a base in grafting reactions of hydroxyl functionalized NHC precursors 6 and 7 with Merrifield PS resins for the preparation of the PSsupported NHC compounds 256 and 257 (Scheme 52). However, the use of a strong base such as NaH and tBuOK is questionable as it can possibly deprotonate the C2 position and lead to undesired side reactions or failure of the immobilization. In addition to halomethyl groups, chlorosilane functionalities have been used in grafting reactions to form silyl ether linkages. Fürstner et al.29 prepared two silica gel supported metathesis Scheme 52. Immobilization of Precursors 6 and 7 by Ether Bond Formation31

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functionalized GO for the synthesis of the GO-supported imidazolium salt 267 from 2 (Scheme 55). It should be noted that the grafting sites in this case were not carboxyl but more stable hydroxyl groups on the GO surface, which were pretreated with p-nitrophenylchloroformate and reacted with 2 to form a carbonate ester bond. In addition to these typical grafting strategies for hydroxyl functionalized NHC compounds, some extraordinary examples of grafting reactions have also been reported. Zhou et al.32 described the preparation of the supported ionic liquid 268 by covalent grafting of diphenolic hydroxyl functionalized imidazolium ligand 8 onto silicon wafers, which were functionalized with silanol groups on the surface (Scheme 56). The immobilization was achieved by formation of a Si−O bond according to a dehydration reaction between a catechol and the surface silanol groups.

grafting process was conducted in the presence of an excess amount of tricyclohexylphosphine as the base for 1.5 h at 25 °C to obtain the supported metathesis catalyst 261. As described by the authors, the as-prepared catalyst 261 could be further encased into a disk shape, which is particularly interesting in the context of high throughput technologies, where monolithic disks serve simultaneously as catalyst support, reaction vessel, and filtration unit. Kühn et al.35 reported on the synthesis of polymer grafted NHC precursor 262 via the reaction between compound 11 and benzoyl chloride functionalized polystyrene (0.8−1.0 mmol of Cl/g) in the presence of a catalytic amount of pyridine in acetonitrile under reflux conditions for 48 h (Scheme 54). The high efficiency of this grafting reaction was evidenced by a model reaction between 11 and benzoyl chloride in homogeneous solution, resulting in quantitative conversion of the hydroxyl group. Since carbon-based materials (e.g., CNT, graphene) can be oxidized to generate carboxyl groups on the surface, the grafting of hydroxyl functionalized NHC compounds to carbon materials by ester bonding is also a practical way to immobilize NHC compounds. In order to achieve a better grafting efficiency under relatively mild reaction conditions, the carboxyl groups of the carbon support are usually further activated by reaction with thionyl chloride or oxalyl chloride.249,259 Liu and co-workers27 described the synthesis of CNT-supported NHC precursor 263 by reaction between the hydroxyl functionalized imidazolium salt 3 and acyl chloride functionalized CNTs in dry THF (Scheme 55). Á lvarez et al.28 prepared CNT-

Scheme 56. Immobilization of Imidazolium Ligand 268 on Silicon Wafers32

Moreover, Dı ́ez-Gonzaĺ ez and co-workers43 immobilized NHC precursor 22 on silica flakes, silica nanoparticles, and magnetic silica nanoparticles and prepared the supported NHC precursors 269−271 (Scheme 57). However, although a

Scheme 55. Synthesis of Carbon Supported NHC Precursors 263−26726−28,260

Scheme 57. Immobilization of Imidazolium Ligand 22 on Silica Flakes, Silica NPs, and MNPs43

covalent binding mode between the hydroxyl group and the silica support was suggested, no detailed explanation of the mechanism of the immobilization or characterization of the immobilized compounds was provided in this study. 2.2.2.2. Grafting via Trialkoxysilyl Group of NHC Moiety. Organosilanes have been used frequently as coupling agents to bind organic functionalities onto the surface of inorganic materials by forming durable Si−O bonds. By introducing trialkoxysilyl functionalities into catalysts, this binding strategy can be applied for their immobilization by covalent grafting onto supporting materials such as silica gel or zeolites, which bear hydroxyl groups on their surface. With respect to NHC compounds, this well-established grafting method is the most frequently applied immobilization strategy to date. As depicted in Scheme 58, trialkoxysilyl functionalized NHC compounds are grafted onto the material surface by Si−O bonding according to a well-established reaction between the trialkoxysilyl groups of the NHC compounds and the hydroxyl groups on the surface of the supports. This anchoring process typically involves the substitution of either one or two alkoxy groups, as hardly ever three surface silanol groups are close enough to bind simultaneously.

supported NHC precursors 264 and 265 (Scheme 55) by treatment of the hydroxyl functionalized imidazolium salts 4 and 17 with acetyl chloride functionalized CNTs in dry THF under reflux conditions. 4 could further be immobilized by reaction with p-nitrophenyl carbonate ester functionalized CNTs in various oxidation states forming 266.260 The benefits of using CNTs as supports lie in their high chemical stability under a large variety of reaction conditions on the one hand and their adequate surface area and controlled porosity on the other hand, which are important properties for catalytic applications.261−263 As an alternative to CNTs, Menéndez and co-workers26 applied p-nitrophenyl carbonate ester V


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conducted at lower temperatures. Reaction times vary between 2 and 48 h. Reported loadings range between 0.040 and 1.600 mmol/g for immobilized imidazolium salts and from 0.013 to 0.534 mmol/g for immobilized NHC complexes (Table 4). Typically, the loadings of imidazolium salts exceed those of the NHC complexes, which may be attributed to the higher solubility and stability of the NHC ligands. However, no underlying trends regarding the resulting NHC loading could be identified, as it is influenced by many factors such as the number of anchor sites, reaction conditions, or the reactivity of the trialkoxysilyl functionalized NHC compounds. The term “amorphous silica” generally refers to silica, which lacks a long-range crystalline order, but may possess a shortrange crystal lattice or even microcrystalline areas. Silica gel is easily accessible, is inexpensive, and is thus frequently used for grafting purposes. For example, NHC precursors 56, 57, 66, 69, 82, and 120 as well as NHC complexes 272−283 have been immobilized onto silica gel (Table 4, Figure 5). Average pore diameters range between 40 and 60 Å, and particle sizes of 60− 23 mesh were reported. Surface areas of 257−550 m2/g were found in some cases.63,85,104 Cai and co-workers observed a decrease in surface area from 546 to 419 m2/g upon immobilization of NHC−Cu complex 283.104 Chung and coworkers, on the other hand, found a slightly increased surface area (257 m2/g compared to 278 m2/g) of 285 after immobilization.85 Additionally, in most cases the silica gel was pretreated by heating under vacuum or calcination at high temperatures under inert atmosphere to remove residual water.63,68,85,93,104 Ö zdemir et al.117 described the pretreatment of silica gel with methanesulfonic acid to increase the amount of silanol groups on the surface for the preparation of NHC complex 292. Buchmeiser and co-workers37 reported the endcapping of the residual silanol groups on the silica surface after immobilization of 120 by (CH3)3SiOCH3 and (CH3)2Si(OCH3)2.

Scheme 58. Grafting of Trialkoxysilyl Functionalized NHC Compounds

The supporting silica-based materials, possessing different textural and physical properties (e.g., shape, morphology, mechanical strength), can be easily prepared by well-established methods or purchased from commercial suppliers. Furthermore, silica materials usually exhibit excellent physical and chemical stability (e.g., high thermal stability, resistance to oxidation), which is crucial for their application as supporting materials. With respect to the immobilization of NHC compounds, three types of silica materialsamorphous silica (e.g., silica gel), ordered meso-silica (e.g., MCM-41, SBA-15), and silica NPsare employed most frequently (Table 4 and Table 5). In a general procedure, the grafting reaction is conducted by stirring of NHC compounds and supporting materials in an aprotic solvent under reflux conditions for 12−24 h. Toluene is the most frequently applied solvent, while the other solvents such as CHCl3, THF, DMF, and CH2Cl2 have only been reported for a few examples. Furthermore, protic solvents such as alcohols or mixed solvent systems of toluene, which can circumvent solubility issues of trialkoxysilyl functionalized compounds in toluene, have been employed in some cases as well. In the presence of water the hydrolysis of the trialkoxysilyl groups is potentially accelerated, which facilitates the formation of the Si−O bond via condensation.87,96,102,127 Nevertheless, the effect of water or wet solvents on the stability of the NHC compounds has to be considered. The syntheses described in this section are mostly carried out under refluxing conditions depending on the solvent used; in a few cases reactions were

Table 4. Immobilization of Trialkoxysilyl Functionalized NHC Compounds onto Silica Gel Support

a

compd

solvent

T (°C)

reaction time (h)

loadinga,b (mmol/g)

120 56 57 57 66 69 82 82 272 273 274 275 276 277 278 274 279 280 281/282 283 274

DCM toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene/DCM CHCl3 CHCl3 CHCl3 CHCl3 benzene benzene 1,2-DCE DMF DMSO

45 105 reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux RT RT 75 120 50

4 10 12 24 − − 24 24 4 4 24 12 20 20 24 24 72 72 24 12 24

0.040a 0.311a 0.890a 0.657a − − 0.401a 0.425a − − 0.029b 0.20b − 0.084b 0.013b 0.066b − − 0.165−0.249b 0.096b 0.086b

supporting material silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica silica

gel gel gel gel gel gel gel gel gel gel gel gel gel gel gel (syn) gel (syn) gel gel gel gel gel

product 28437 28585 28689 28793,95 288103 289103 29093 29193 292117 293264 29479 295106 296103 297103 298119 299119 30063 30163 302/30368 304104 30580

Loading of imidazolium salt. bMetal loading. W


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Figure 5. Examples of NHC−metal complexes used for grafting onto silica gel.63,68,79,103,104,106,119,264

Table 5. Immobilization of Trialkoxysilyl Functionalized NHC Compounds onto Ordered Mesoporous Silica Materials

a

compd

solvent

T (°C)

reaction time (h)

loadinga,b (mmol/g)

supporting material

product

57 306 306 306 309 310 311 312 313 314 315 306/316−317 318−320 275 318 319 320 321 322 57 76 105 323 325 324 326 323 327 328 329 274/56 330 274/56 310

toluene toluene toluene toluene toluene toluene toluene toluene/EtOH toluene/EtOH toluene/EtOH toluene/EtOH toluene/EtOH toluene/DCM toluene/DCM DCM DCM DCM DCM toluene toluene toluene toluene/CHCl3 toluene toluene toluene toluene toluene toluene toluene toluene toluene/EtOH DMF CHCl3 toluene

105 100 100 100 reflux reflux reflux 100 100 100 100 100 110 reflux RT RT RT RT reflux reflux reflux reflux RT 80 80 reflux reflux reflux reflux reflux 70 130 reflux reflux

12 12 12 12 16 24 24 6 6 6 6 6 16 12 24 24 24 24 22 24 2 9 48 12 12 12 24 24 48 48 20 24 32 24

0.750a 0.06−0.08b 0.06−0.08b 0.06−0.08b 0.060b 0.093b 0.158 (cal)b 0.060b 0.090b 0.060b 0.060b 0.070−0.100b 0.038−0.081b 0.21b 0.130b 0.155b 0.092b 0.149b 0.15b 1.600a − − 0.069b 0.075b 0.052b 0.228b 0.088b 0.100b − 0.039−0.198b 0.076b − 0.021b 0.053b

MCM-41 MCM-41 MCM-41/Sn MCM-41/Al MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 MCM-41 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-15 SBA-16 KIT-6

33190 332127 333127 334127 335128 33696 337115 338126 339126 340126 341126 342/343−344129 345−347124,125 348106 349101 350101 351101 352101 353265 35481 355112 356131 35740 360111 361111 362266 36340 36465 365113 366118 36788 36898 36983 37096

Loading of imidazolium salt. bMetal loading.

large specific surface areas and uniform, tunable pore sizes are currently more frequently used as well-defined supports (Table 5). Among various types of mesoporous silica materials, MCM41 and SBA-15 are the two most representative and widely used

Difficulties regarding the characterization of amorphous silica based compounds and investigation of their catalytic performance may arise from the irregular structure of the material including large distributions in pore diameters and void volumes. Therefore, ordered mesoporous silica materials with X


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Figure 6. Examples of NHC−metal complexes used for grafting onto MCM-41.65,101,115,124−128,265

SBA-15 (Santa Barbara Airport No. 15), which was first synthesized by Stucky and Zhao et al.267 at the University of California, Santa Barbara, is another easily prepared, mesoporous silica material with high specific surface areas typically ranging from 690 to 1040 m2/g. Compared to MCM-41, SBA15 has larger pore sizes ranging from 4.6 to 30 nm. This feature can be adjusted easily by adjusting the length of the hydrophobic part of the surfactant or the reaction temperature during the synthesis.267 Moreover, SBA-15 has thicker pore walls (3.1−6.4 nm) than MCM-41 ( 470 > 471 > 472). In contrast to that, the prequaternized imidazolium salts exhibited higher surface areas with longer substituent chains (469 < 470 < 471 < 472). Additionally, despite the hexagonal mesostructure of the precursor compound 468, the postalkylated silica compounds 469−471 all yielded mesoporous silica, while only 472 synthesized by direct co-condensation was found with a well-defined hexagonal nanostructure. This might be attributed to the fact that a hydrophobic hydrocarbon chain

Immobilization by organic polymerization is a perfect example for self-supporting methods, as it shows the main advantages of this approach. In a polymerization essay, the distribution and density of the active centers within the material can easily be controlled by the composition of the reaction mixture and the reaction protocol in a simple and straightforward procedure. Typical examples are the ruthenium catalyzed ROMP of norbornene bearing NHC precursors or copolymerization of alkenes with vinyl substituted imidazolium salts. Going from simple polymer networks to covalent organic frameworks, one gains the advantages of the highly ordered porous structure, which is a key feature of these materials. Prominent synthetic pathways are the quaternization of bis(imidazolium) structures with multivalent halide precursors and polymerization via cross-coupling. AI


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Hesemann et al. for the synthesis of 474. Besides the use of TEOS, bis(triethoxysilyl)ethane (BTEE) was employed as the cross-linking reagent for the syntheses of the silica supported NHC precursors 475 and 477. To prepare the SBA-15 type silica compound 475, 112 was co-condensed with BTEE at ratios going from 1/19 to 1/4 in a solvent mixture of H2O and ethanol using P-123 as the template reagent.133 It was found that the specific surface area of 475 decreased from 1040 to 681 m2/g with increasing molar fraction of 112 (5−20%). Interestingly the silica compound 475, which was prepared by using 112 in the highest molar fraction of 20%, was still obtained as a highly ordered hexagonal mesoporous material. 477 was synthesized by co-condensing BTEE with the triethoxysilyl functionalized NHC precursor 113 in the presence of template agent F127.135 It was observed that the molar ratio of 1/4 for 113/BTEE was the upper limit for the loading with NHC precursors that still allowed 477 to have a high surface area of 743 m2/g as well as a large pore size of 4 nm. When comparing the syntheses of 475, 476, and 477, it appears that the use of BTEE allows a higher loading of the NHC precursor incorporated into the mesoporous materials than in the case of TEOS. This may be attributed to different interactions between the siliceous precursor and the template.135 Ritleng and co-workers112 prepared the SBA type silica compound 478 by sol−gel synthesis, reacting the triethoxysilyl functionalized NHC precursor 76 with TEOS in the presence of P-123 under acidic conditions (Scheme 89). The obtained

would assist the micellar arrangement of the surfactant molecules in the sol−gel reaction. In 2009, the same group reported another work on sol−gel syntheses of organosilica supported NHC precursors 473 and 474 from triethoxysilyl functionalized NHC compound 112.132 In order to prepare the supported NHC ligand 473 via polycondensation of 112, various template surfactants (e.g., P123, CTAB) and reaction media were tested (Scheme 88). It Scheme 88. Sol−Gel Syntheses of the Immobilized NHC Precursors Based on 112 and 113132,134,135

was found that the substructure of 112 is preserved under neutral and acidic reaction conditions, while decomposition of the material occurs in basic media. The highest surface area of 104 m2/g was obtained by using the nonionic surfactants P-123 in acidic reaction media. Based on this evaluation of reaction conditions, further preparation of the periodic mesoporous organosilica material (PMO) 474 was carried out by cocondensation of 112 and TEOS with P-123 as the template compound in acidic reaction media. Various molar ratios of 112 and TEOS (112/TEOS from 1/9 to 1/2) were used to form the porous material 474 with different structural features and NHC precursor loading levels. The surface areas and pore diameters of 474 were ranging from 720 to 1170 m2/g and from 4.0 to 7.2 nm, respectively. The highest surface area of 474 was obtained by using 112/TEOS of 1/4, while the highest pore size was achieved by using 112/TEOS of 1/6. It is also worth mentioning, that the structural regularity of 474 decreased with increasing amount of incorporated NHC precursors. A similar strategy was also used by Yang et al.134 in a series of publications for the syntheses of mesoporous silica supported NHC precursors 475−477 (Scheme 88). The NHC precursor 476, supported by cagelike cubic mesoporous silica (SBA-16 type), was synthesized using a mixed surfactant system of F127 and small amounts of P-123 as the template reagents for the cocondensation of TEOS and 112. Furthermore, a certain amount of ethanol was added to the reaction mixture to dissolve 112 in TEOS, since phase separation would lead to the formation of inhomogeneous materials. Since the ratio of reactants significantly influences the final hybrid materials, the molar ratio of 112/TEOS was also varied over a broad range going from 1/78 to 1/11. It was found that the highest surface area (753 m2/g) and pore size (5.5 nm) of 476 were obtained employing the lowest 112/TEOS ratio of 1/78. Moreover, a higher amount of 112 was found to deteriorate the mesostructural ordering, which is similar to findings by

Scheme 89. Preparation of the Organosilica Supported Imidazolium Compound 478112

mesoporous material 478 presented a surface area of 555 m2/g and an average pore size of 6.7 nm but did not exhibit a longrange ordering, which can be attributed to the incorporation of the NHC precursor. With a site-selective acidic sol−gel process, Pleixats et al.107 reported the syntheses of mesoporous silica (MCM-41) supported imidazolium salts 479 and 480 (Scheme 90). The group used NaBF4 as a promoter and 1-cetyl-3-methylimidazolium chloride as cationic surfactant for the condensation of TEOS and triethoxysilyl functionalized NHC compounds 68 and 87, respectively. 479 was obtained as MCM-41 type mesoporous silica with a surface area of 506 m2/g, while 480 was prepared as a wormlike mesoporous structure with a relatively low surface area of 266 m2/g. Moreover, 87 was also (homo)polymerized without TEOS in neutral reaction conditions with the same promoter and surfactant to afford a nonporous silica material with a very low surface area of 2 m2/g. Direct hydrolysis and polycondensation of bistrimethoxysilyl functionalized NHC precursor 86 under mildly acidic conditions afforded the supported-NHC precursor 481 as a yellow solid (Scheme 91).120 However, no other details on its structure were given in this study. AJ


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Scheme 90. Synthetic Procedure for the Preparation of 479 and 480107

Scheme 93. Preparation of the Immobilized NHC−Pd Complexes 484, 487−488, and 493−49694,108,121

Scheme 91. Synthesis of 481 by Simultaneous Hydrolysis and Polycondensation120

Apart from those syntheses of pure mesoporous silica materials, the preparation of silica coated MNPs 482, which are functionalized with NHC precursors (Scheme 92), has also Scheme 92. Preparation of the Organosilica Coated Magnetic Nanoparticles 482297

base catalyzed reaction conditions.298 However, the obtained hybrid material exhibited a low porosity and a surface area of 5 m2/g. Similar reaction conditions, using NH4F as catalyst, were described for the syntheses of mesoporous silica supported NHC−Pd complexes 487 and 488 (Scheme 93).108 These were prepared by reacting the corresponding trialkoxysilyl functionalized NHC−Pd complexes 485 and 486 with TEOS in a mixture of DMF and water. Both resulting compounds were obtained as mesoporous hybrid silica materials with high surface areas of 730 and 810 m2/g, respectively. It is noteworthy that the ancillary ligand of the NHC−Pd complexes induced different textural properties in their final hybrid materials; e.g., 487 showed a narrower pore size distribution as well as a smaller pore size than 488. Further, the bis-carbenes 489−492 and a siloxy functionalized ionic liquid were reacted with TEOS in a mixture of methanol and water to yield the silica supported carbene compounds 493− 496 (Scheme 93).94 It was found that these products possessed a 2D hexagonal symmetry, presenting an MCM-41 type mesoporous structure. Moreover, the intensities of diffraction peaks corresponding to the periodic channels of these compounds became weaker from 493 to 496 due to the increasing length of the alkyl chain of the N-substituent. It should be noted that the introduction of the IL may enhance the selectivity of those silica compounds due to a diffusion control effect. In addition to NHC−Pd complexes, the same authors also reported the use of trialkoxysilyl functionalized NHC−Ru and

been reported.297 In this study, reverse micelles with iron oxide cores were prepared initially and coated consecutively by cocondensation of 113 with TEOS in aqueous solution, synthesizing a mesoporous silica shell around the iron oxide NPs. The as-prepared particles were found with a size distribution of 15−30 nm and surface areas ranging from 206 to 265 m2/g. These properties were tunable by varying the amount of siliceous precursors used; i.e., a higher amount leads to a larger particle size and a lower surface area. Apart from NHC precursors, NHC−metal complexes with trialkoxysilyl functionalities were also used to prepare hybrid silica materials with NHC complexes via sol−gel processes. Hesemann and co-workers121 reported on a silica-supported Pd−NHC complex 484 prepared through sol−gel condensation of the triethoxysilyl functionalized Pd−NHC complex 483 (Scheme 93). Due to the poor stability of 483 in basic media, the synthesis of 484 was conducted in a mixture of THF and water at room temperature. The reaction was catalyzed by fluoride ions (NH4F) instead of the typically applied, acid or AK


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−Rh complexes 497, 499, and 501 to prepare the respective hybrid silica materials 498, 500, and 502 (Scheme 94). To

Scheme 95. α-Zirconium Phosphonate Based NHC Precursors 539−540187

Scheme 94. Sol−Gel Synthesis of 498, 500, and 502 Using TEOS64,65

these systems is the highly controllable structure of the products that can be tuned by, e.g., varying the reaction temperature, solvent composition, or the surfactant type. Moreover, the sol−gel process allows a homogeneous distribution of active centers. The synthesis via co-condensation of TEOS with alkoxysilane functionalized imidazoles or imidazolium salts proceeds under relatively mild conditions and even allows the immobilization of already metalated NHC complexes. 2.2.3.3. Formation of Coordination Polymers. In general, coordination polymers are considered as metal−organic assemblies with one-, two, or three-dimensional (1D, 2D, or 3D) coordination geometry, such as linear-coordination polymers or coordination networks (e.g., metal−organic frameworks (MOFs)).299 They are usually prepared by forming coordination bonds between ditopic (or polytopic) ligands and metal atoms. The resulting solid compounds may have their catalytically active centers either located at the metal node or on the organic backbones. For NHC compounds, the formation of coordination polymers is a useful self-supported method to obtain immobilized catalysts without using separate supports. In general, the linkage of monomers for the polymerization of NHC compounds can be achieved through the carbene functionality itself (i.e., the generation of biscarbenes) or through a different moiety in the molecular backbone. In 1997, Bertrand et al.300 reported a light-sensitive organometallic polymer that was based on a 1,2,4-triazole carbene−Ag complex. This was the first NHC−metal coordination polymer with a well-defined crystal structure (Scheme 96) and opened the gates for the development of metal coordination polymers by stable carbene functionalities.

prepare the silica supported metathesis catalyst 498, a mixture of 497 and TEOS in a ratio of 1/38 was co-condensed in DMF solution using TBAF as the catalyst.64 The as-obtained material, which had a surface area of 404 m2/g and an average pore size of 2.3 nm, was found to possess both micropores and mesopores. With the same synthetic method, the Rh−NHC complexes 500 and 502 were also transformed into silica hybrid materials.65 By tuning the 499/TEOS ratio, the hybrid material 500 could be prepared as a microporous material (1/14) as well as a mesoporous material (1/30) with surface areas of 453 and 493 m2/g, respectively. Meanwhile, the mesoporous silica compound 502 with a surface area of 325 m2/g was prepared by using 501/TEOS in a ratio of 1/30 (Scheme 94). It is worth mentioning that partial decomposition of the NHC metal complexes during the formation of the hybrid materials via the sol−gel process has been observed for several cases.64,65,108 In analogy to the use of trialkoxysilyl functionalized NHC compounds, the α-zirconium phosphonate (ZrP) supported NHC precursors 539 and 540 are examples for self-supported, immobilized NHC compounds (Scheme 95). The phosphonate ester functionalized NHC ligands 182 or 183 and a 4bromobutyl phosphonate ester were subjected to hydrolysis under acidic conditions followed by a hydrothermal reaction with ZrOCl2 in the presence of HF.187 The α-zirconium phosphonate supported NHC precursors were both obtained as a white solid with layered structures and could further react with different metal precursors such as [Ir(COD)Cl]2 and [Rh(COD)Cl]2 to prepare α-zirconium phosphonate supported NHC−metal complexes. As can be seen from the above-mentioned examples, the use of silyl functionalized NHC compounds is a well-established strategy toward their immobilization. The major advantage of

Scheme 96. Synthesis of Silver 1,2,4-Triazole Polymer According to Bertrand et al.300

In 2005 Bielawski and co-workers161 reported a series of publications on the preparation of the NHC−metal coordination polymers 503−513 using the corresponding opposedditopic bis-NHC compounds 143−154 (Scheme 97). The ditopic NHC precursors were reacted with the corresponding metal precursors such as Pd(OAc)2 and PtCl2 in DMSO solution at elevated temperatures (80−110 °C) for 1−48 h. All the polymers were obtained in high yields (>88%) and with molecular weights (Mn) varying from 8.0 × 103 to 1.8 × 106 g/ mol, depending on the ligands and metal precursors used. AL


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Recently, Tu et al.166 reported the polymerization of iridium precursors (e.g., [Ir(COD)Cl]2, [Ir(COD)OMe]2) with the bis-NHC compounds 143 and 148 in the presence of an external base under heating, thus preparing the NHC−Ir coordination polymers 515−520 (Scheme 99) in high yields

Scheme 97. Copolymerization of 143−154 with Pd and Ni Precursors To Yield Their Respective Organometallic Polymers161,163,165,167

Scheme 99. Preparation of Ir Coordination Polymers 515− 520166

(93−99%). These polymeric compounds were found insoluble in all common organic solvents as well as water, were air and moisture stable, and even remained intact after heating at 100 °C in water for 120 h. With these features, 515−520 were successfully employed as robust recyclable self-supported catalysts for oxidative transformation of glycerol to potassium lactate. A rather unusual polymerization method was presented by Lee et al.,169 who prepared the polymeric Hoveyda−Grubbstype NHC−Ru compound 522 by a ligand exchange reaction between the dimeric Ru−NHC complex 521 and the isopropoxystyrene linker (Scheme 100). The polymerization reaction was conducted by mixing 521 and the linker (1/1 molar ratio) in the presence of CuCl in DCM at 40 °C for 12 h, yielding 522 as an oligomeric compound. Moreover, it was found that 522 was soluble in chloroform and dichloromethane but insoluble in toluene and ethyl acetate, which indicated that this polymeric compound could be recovered by precipitation. Besides those ditopic NHC ligands, the tritopic NHC compound 155 was also used to react with Pd(OAc)2 in DMF solution at 110 °C for 48 h producing the triptycenebased NHC−Pd coordination polymer 523 (Scheme 101) in a high yield of 95%.168 Unlike the linear coordination polymers obtained by ditopic ligands, 525 was obtained as a microporous polymer in a spherical and irregular shape with a BET surface area of 464 m2/g. An even more complex network was achieved by using the adamantane based tetraimidazolium salt 524 (Scheme 102), which was polymerized with Pd(OAc)2 in DMF yielding the polymeric NHC compound 525. 301 The amorphous, porous product was found to contain mainly micropores and possessed a BET surface area of 54 m2/g. The polymer was then applied in the Pd-catalyzed Suzuki−Miyaura reaction. In addition to the carbene functionality, coordination polymerization through other functional groups of the NHC ligand is another feasible approach to generate polymeric NHC complexes. MOFs, which are prepared by joining organic linkers and metal-containing units (e.g., inorganic metal ions, metal ion clusters) via reticular synthesis, are tunable porous coordination polymers that can be used for various applications such as catalysis, drug delivery, sensing, gas storage, and separation.302−304 The development of MOF-based NHC compounds has hence attracted considerable interest (Table 7). Son and co-workers137 reported the first example of organometallic NHC−metal complexes within a MOF structure by using the dicarboxyl functionalized NHC ligand

Furthermore, these polymers were soluble in highly polar aprotic solvents such as DMSO, DMF, and NMP. On the basis of this work, the polymeric NHC−Pd complex 503 (Scheme 97) bearing a benzyl group was reported as an effective and reusable catalyst for the Suzuki−Miyaura coupling reaction in water (for catalytic performance see section 4.2.1).163 The same group also tested the polymeric NHC− Pd compounds 505 and 508 featuring hexyl and dodecyl chains as N-substituents. Comparing the catalytic performances of these two compounds with 503, they found that 508 was the most active and recoverable in the aqueous Suzuki−Miyaura reaction. This was attributed to the more lipophilic character of the dodecyl substituent. Following these results, the TEG functionalized imidazolium salt 147 was synthesized for the preparation of the water-soluble polymeric NHC−Pd complex 507 under the same reaction conditions.165 The newly designed water-soluble catalyst 507, which had an average molecular weight (Mn) of 1.1 × 105 g/mol, showed a higher activity and recyclability for the aqueous Suzuki−Miyaura coupling reaction than its water-insoluble analogue 503. The major reason for this increased catalytic activity certainly lies in its good water solubility, which allowed the catalysts to remain in the reaction mixture instead of being lost gradually by filtration as in the case of 503. Moreover, 507 also exhibited good solubility in dipolar aprotic solvents such as DMF and DMSO and could be collected in pure form by using a simple dialysis technique. Furthermore, polymeric NHC−Pd compound 514 could be prepared via a two-step synthesis by using an external base to deprotonate 150 followed by addition of PdCl2 as reported by Bielawski et al. (Scheme 98)162 Scheme 98. Two-Step Synthesis To Prepare Metal−Organic Polymer 514162

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Scheme 100. Synthesis of Polymeric Hoveyda−Grubbs-Type NHC−Ru Compound 522169

Scheme 101. Polymerization of tritopic NHC Precursor 155 To Generate the Coordination Polymer 523168

Table 7. Schematic Representation of Immobilized NHC Compounds and Reaction Conditions Used during Their Synthesis137,140−144,305

Scheme 102. Tetraimidazolium Salt 524 Used for the Polymerization with Pd(OAc)2 To Yield the Polymeric NHC Compound 525301

linker

reaction conditions

product

133 133 133 133 131 127 127

Cd(NO3)2, 110 °C, DMF Cu(NO3)2, 110 °C, DMF Ce(NO3)2, 110 °C, DMF Ce(NO3)2,Cu2O, 110 °C, DMF Zn(NO3)2, Cu(CH3CN)4PF6, DMF Zn(BF4)2, KPF6, 100 °C, DMF 1. Pd(CH3CN)2Cl2 2. Zn(NO3)2, 100 °C, DEF/pyridine Cu(NO3)2, 65 °C, MeOH/EtOH Zn(NO3)2, RT, H2O/EtOH

526137 527137 528305 529305 530143,144 532142 534142

125 126

535140 536141

within the structure, while the Cu(II) species coordinated to the carboxylates. This did not apply to cadmium complex 526, which required the addition of a base to deprotonate the imidazolium salt. On the basis of this result, the same group described another set of Cu−NHC MOF complexes 528 and 529, which had 3D networks constructed by cerium nitrate and 133.305 The syntheses of 528 and 529 were similar to those of 526 and 527, with the sole difference that Cu2O was used as additional metal source in the preparation of 529 to incorporate NHC−copper species into the polymeric network. It should be noted that the NHC−copper moieties were not formed for all building units but for every second building unit in each helical chain balancing the charge of 529. Sumby et al.143,144 reported the use of the dicarboxyl functionalized NHC precursors 131 and 132 (Scheme 17) to construct MOF-tethered NHC compounds. By solvothermal treatment of a mixture of 131, Zn(NO3)2·6H2O, and [Cu(CH3CN)4]PF6 in DMF solution at 120 °C for 14 days, the three-dimensional MOF compound 530 with Cu(I) bisNHC units was prepared. Single crystal X-ray diffraction indicated that 530 possesses a diamondoid 3D framework, which was constructed from a Zn4O node and a Cu(I) bis-

133 (Scheme 17). Various transition-metal salts such as zinc, manganese, cobalt, and cadmium nitrates were tested as connectors to synthesize self-assembled polymeric compounds. However, only cadmium nitrate and copper nitrate were successfully reacted with 133 to prepare the respective MOFbased NHC compounds 526 and 527. In these syntheses, ligand 133 and the corresponding metal precursor were dissolved in DMF solution and heated at 110 °C for 3 or 5 days to prepare MOF complexes in good yields (54−74%). Interestingly, the Cu complex 527 contained two different copper species, Cu(I) and Cu(II). The Cu(I) species coordinated to the carbene functionality of the NHC moiety AN


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mixed solvent system of EtOH and H2O at room temperature for 3 days. An intriguing feature of 536 is the single-walled chiral MONT (metal−organic nanotube) structure, which is formed by double helices with an interior channel diameter of 3.32 nm and an exterior wall diameter of 4.91 nm. Remarkably, the two methyl groups introduced induced a bent geometry of the bis-NHC ligand, therefore directing the metal−ligand orientation toward the formation of discrete MONTs. Furthermore, this MOF compound could also be postsynthetically modified by transformation of the imidazolium moieties with metal precursors such as Pd(OAc)2. Hupp and co-workers306 reported an unusual MOF structure, 538, which was composed of metal imidazolates rather than imidazolium salts.307 As shown in Scheme 104, the

NHC linker. Furthermore, 530 was thermally stable up to 400 °C, while its structure collapsed upon desolvation as revealed by thermogravimetric analysis and powder X-ray diffraction experiments. The treatment of 132 with zinc nitrate in DMF solution at 120 °C for 5 days only afforded a 1D coordination polymer 531 rather than a 3D MOF network (Scheme 103).144 Scheme 103. Synthesis of 1D Coordination Polymer 531144

Scheme 104. Metal Imidazolate Based MOF Structure 538, Obtained by Polymerization of Co Salts with 537306

Yaghi and co-workers142 reported a different synthetic method to prepare the MOF-supported imidazolium salt 532 and the corresponding NHC−Pd complex 534 starting from the linear dicarboxyl functionalized NHC compound 127 (Scheme 16). In this study, two synthetic routes from different initial building blocks have been tested. First, 127 was initially transferred into its BF4 analogue, which was then used to react with Zn(BF4)2·H2O in DMF solution at 100 °C for 36 h, synthesizing the MOF-supported NHC compound 532. However, 532 could not be transformed to the respective NHC−Pd complex by various synthetic methods, e.g. base deprotonation synthesis or transmetalation of the silver complex. The second route comprised formation of the Pd− NHC complex 533 from 127, which was further reacted with Zn(NO3)2·6H2O in a solvent mixture of N,N-diethylformamide (DEF) and pyridine (75/1) at 100 °C for 30 h. The resulting NHC−Pd bearing MOF structure 534 displayed a surface area of 1590 m2/g and a pore aperture of ca. 5 Å × 10 Å. Furthermore, single crystal X-ray diffraction indicated a MOF-5 type structure of 534, and confirmed the presence of the NHC−PdI2(pyridine) moiety within the framework. The dicarboxylated bis-NHC precursor 125 (Scheme 16) was used to prepare the 3D MOF complex 535, which could be modified postsynthetically with catalytically active NHC functionalities.140 The synthesis of 535 was conducted by heating a mixture of 125 (1 equiv) and Cu(NO3)2·3H2O (5 equiv) in a mixture of MeOH and EtOH at 65 °C for 1 day. The crystal structure revealed a distorted square-pyramidal geometry of 535, with each Cu(II) atom being coordinated by four carboxyl groups from four individual linkers and one MeOH. Further postmodification of 535 with Pd(OAc)2 in THF was successful, and it was found that 76% of the NHC sites in 535 were bearing a Pd atom. It is worth mentioning that the reaction between 125 and CuCl2·2H2O in EtOH resulted in a linear coordination polymer, which could also be functionalized with metal atoms via their NHC moieties. By using the modified dicarboxylated bis-NHC precursor 126, the same group described another NHC−MOF structure (536) in a subsequent work.141 The synthesis of 536 succeeded via the reaction between 126 (Scheme 16) and Zn(NO3)2·6H2O in a

preparation of 538 was accomplished by the reaction of the tripodal imidazole compound 537 (1 equiv) and CoCl2·6H2O (1 equiv) in a solvent mixture of DMF, ethylene glycol, and pyridine at 140 °C for 72 h. The crystal structure of 538 revealed that each imidazole coordinated to one cobalt atom creating two interweaving two-dimensional sheets, which formed one-dimensional channels perpendicular to the plane with a diameter of 8.5 Å. By addition of n-butyl lithium to 538, the imidazolate species were successfully deprotonated to generate exposed NHC sites within the MOF structure. These deprotonated species could serve as Brønsted-base-type NHC catalysts for conjugated addition reactions. Concluding the results reviewed, coordination polymers constitute a very interesting group of immobilized NHC compounds since, in many cases, the influence of the supporting material is very little. This is the case for coordination polymers that only consist of bis- or multi-NHC ligands and the desired metal atom and renders them highly attractive as catalyst materials. Alternatively, classical MOF structures can be synthesized bearing NHC precursors, which can then again act as supports. By preparing these coordination polymers, interesting microstructures can be achieved, yet, at the cost of more tedious synthetic planning. 2.2.4. Formation of NHC Stabilized Metal NPs. NHCs are neutral, σ-donating ligands, which usually form strong metal−ligand bonds in complexes. Hence, they are also capable of binding directly to metallic colloids or surfaces to prepare functionalized heterogeneous metallic materials.4 The idea that the strong and stable NHC−metal bond may prevent NPs from agglomeration gave rise to a great interest in NHC-modified metal NPs in recent times.197 Surfaces, however, representing infinite systems are beyond the scope of this review, and deeper insight into this subject can be gained from a review by Johnson et al.197 Up to now, two synthetic approaches are commonly used to prepare NHC-stabilized NPs (Figure 9).308 AO


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Scheme 106. Synthesis of Au-NPs Stabilized by Amphiphilic Imidazolium Salts153

Figure 9. Two possible approaches to prepare NHC stabilized metal NPs.308

One method, mostly reported in early examples, is the controlled selective degradation of the corresponding metal complexes. In this method, reduction agents such as H2, NaBH4, or KBEt3H are usually employed to reduce the metal ion of the complex to form metal NPs, which are then stabilized by the afore-coordinated NHC ligands. Tilley et al.309 showed that NHC-stabilized Au-NPs could be obtained by reduction of NHC complex 541 at room temperature with KBEt3H or 9BBN (9-borabicyclo[3.3.1]nonane) in THF or Et2O solution, respectively, within 40 min (Scheme 105). The NPs 542

Scheme 107. Preparation of NHC Bearing Ru-NPs via the Decomposition of [Ru(COD)(COT)] in the Presence of 546−547310

Scheme 105. Synthesis of NHC Stabilized Gold NPs through the Reduction Route, Starting from 541309 state under anaerobic conditions and the carbene ligands on the surface were not displaced by diphosphines or thiols in solution. 548−549 were later used in catalytic hydrogenation reactions, and it was found that the activity of the NPs 548− 549 was mainly influenced by the substituents of the NHC ligand.311 The same synthetic strategy was also successfully applied for the synthesis of NHC stabilized Pt-NPs using the free NHCs (550 or 551) and Pt(dba)2 (Scheme 108).312 The Scheme 108. Synthesis of Pt-NPs 552/553312

prepared by using KBEt3H as reducing agent exhibited a broad size distribution with diameters of 6.8 ± 1.8 nm, whereas monodispersed NPs 543 in the domain of 5.75 nm were synthesized by employing 9-BBN. Furthermore, this work also indicated that the size of NPs could not only be controlled by the NHC/metal ratio, but also by the nature of the substituents on the NHC ligand. With bulky and rigid isopropyl substituents, the NPs were obtained in a smaller size of ∼2 nm compared to that of complex 542 with flexible, long linear alkyl chains on the NHC moiety (6−7 nm). In another reported example, gold NPs were synthesized from HAuCl4 and NaBH4 in the presence of 134, yielding monosdisperse NPs 545 with diameters between 3.7 and 5.9 nm (Scheme 106).153 As shown by SPR and IR measurements 134 acted as a surfactant on the Au surface, but the absence of Au(I) peaks in XPS spectra suggested that the binding to the gold NPs did not occur via a carbene bond. Chaudret and co-workers310 reported the synthesis of NHC stabilized Ru-NPs by decomposition of [Ru(COD)(COT)] in the presence of free NHCs (546 or 547) in pentane solution with H2 at room temperature (Scheme 107). The Ru-NPs 548−549 were prepared in different particle sizes (1.2−1.7 nm) by using different NHC ligands and NHC/metal ratios. It was found that a higher NHC/metal ratio led to smaller particles. Furthermore, all NPs were stable in solution as well as in solid

as-prepared NPs 552 and 553 were obtained in mean diameters ranging from 1.6 to 2.0 nm. Similarly, this work also observed the same phenomenon described by Chaudret concerning the size of NPs, which could be influenced by the NHC ligand as well as the NHC/metal ratio used.310 Pileni and co-workers313 described the syntheses of crystalline Ag- and Au-NPs 560−565 from Ag− and Au− NHC complexes 554−559 by decomposition methods (Scheme 109). In this work, ammonia boranes (NH3BH3 and t BuNH2BH3) were employed as reduction agents and dodecanethiol (DDT) was introduced as an additional stabilizing agent. In a typical synthesis, the NHC−Au complex and DDT were mixed in toluene and heated at 100 °C for 0.5 h prior to the addition of the reduction agent. The reaction mixture was further stirred for another 0.5 h to eventually obtain the corresponding crystalline Au-NPs. Interestingly, the addition sequence of the reactants would significantly affect the formation of the Au and Ag nanocrystals. The reactions, in which the reduction agent was added prior to DDT, were usually unsuccessful especially when NHC−Ag complexes were AP


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Scheme 109. Preparation of Crystalline NHC-Bearing Auand Ag-NPs through Reduction with Ammonia Boranes313

Scheme 111. Synthesis of the Water-Soluble Pt-NPs 572− 575192

used. The Au-NPs were prepared in narrow size distributions (standard deviation 4.6−6.7%) with average sizes of 6.3− 6.7 nm except for the NPs stabilized by the ligand bearing the most sterically demanding substituent (DiPP), which had an average diameter of 2.7 nm. With Ag derivatives, the NPs were obtained in similar average sizes ranging from 6.3 to 6.7 nm with slightly larger size distributions (standard deviation 7.2− 9.2%). The Au-NPs 567 (Scheme 110), which were stabilized by a PEGylated NHC ligand, were synthesized by degradation of

without precipitation or agglomeration of Pt(0) for several months. Apart from using NHC metal complexes as precursors, imidazolium metalate salts were also reported as starting materials for the synthesis of NHC-stabilized NPs in the presence of a base and a reducing agent. The Au-NPs 578 and Pd-NPs 579 were synthesized from the respective imidazolium metalate precursors 576 and 577 (Scheme 112).315 The Scheme 112. Synthesis of NHC-Stabilized NPs from Their Imidazolium Metalates315

Scheme 110. Synthesis of Gold-NPs Functionalized with PEG Bearing NHC Ligands314

syntheses were carried out by treating the corresponding imidazolium salt with a base (NaH) in a solvent mixture of DCM and toluene, before adding the reducing agent (NaBH4). The Au-NPs 578 were polydisperse and had large particle sizes of ca. 16.6 nm, while the Pd-NPs 579 were generated monodispersely with small particle sizes of ca. 2.7 nm. In a recent work Pileni et al.316 also reported a synthesis of crystalline Au-NPs 585−589 from imidazolium metalate salts (Scheme 113). In this study, five imidazolium salts 580−584 with different types of substituents were tested in the same synthetic procedure, during which the imidazolium salt was first deprotonated by NaH in a mixed solvent of DCM and toluene

NHC−Au complexes 566.314 These NPs, which had a core− shell diameter of 14.6−20.8 nm, were found stable toward aggregation and compatible with various conditions such as aqueous solutions in the pH range 3−14, aqueous H2O2 solutions, and cell culture media. To synthesize 567, the Au complex 566 was exposed to tert-butyl amino borane in THF solution for 24 h prior to dialysis against water for an additional 24 h. It should be noted that complex 566 was not a pure Au(I) complex but a mixture of Au(I) and Au(III) complexes, as these two complexes were generated in a one-pot synthesis and could not be separated. One special example reported by Chaudret and co-workers192 was the preparation of water-soluble Pt-NPs 572−575 without using any reduction agent but by thermally activated ethane elimination of dimethyl NHC−Pt complexes 568−571 (Scheme 111). The synthesis of the Pt-NPs was initiated by stirring and heating the solution of the corresponding Pt complex in deionized water at 80 °C for 18 h. Further dialysis of the initially formed Pt-NPs by using a cellulose membrane yielded 572−575 in a fairly uniform spherical shape with diameters ranging from 1.3 to 2.0 nm. The use of bulky NHC ligands induces small particle sizes, and colloidal suspensions of 572−575 in water were quite stable in air and highly dispersed

Scheme 113. Preparation of NHC Functionalized Crystalline Gold NPs with Long Alkyl Chains in the NHC Backbone316

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followed by dropwise addition of an aqueous solution of NaBH4 at 0.6 °C. Au-NPs 585−589 were obtained in different average sizes ranging from 3.5 to 5.9 nm, and it was found that the particle sizes are influenced by the position as well as combination of the alkyl chains of the NHC moieties. Moreover, the Au-NPs with a size of 5 nm could be further transformed into thick and large 3D supracrystal domains via an assembly processes. The second method to prepare NHC-stabilized NPs is by ligand exchange with NPs protected by a sacrificial labile ligand (Figure 9). Chechik and co-workers317 first reported the synthesis of Au-NPs 590 by the ligand exchange method (Scheme 114). In this work, a 200-fold excess of free NHC 546

exchange with the NHCs could not be complete but resulted in a mixed ligand environment. TEM measurements revealed that 593 had a particle size similar to that of the thioether stabilized NPs (4.5 nm), which indicated that no aggregation took place during the exchange reaction. It is worth mentioning that 593 was stable over 4 months and could be handled in air. Furthermore, according to additional control experiments, NHCs with small substituents were found to be preferable for preparing stable NPs via the ligand exchange method. Besides the two widely used methods mentioned above, some other synthetic approaches are also reported to prepare NHC-stabilized NPs. The formation of the magnetite supported Pd-NPs 596 (Scheme 116) was conducted by direct

Scheme 114. Addition of NHC Ligands onto Au-NPs through Ligand Exchange317

Scheme 116. Synthesis of Magnetite Supported Pd-NPs Stabilized by Chiral NHC Ligand 595318

was added to the benzene solution of thioether stabilized AuNPs and the reaction mixture was left to precipitate for 12 h without stirring. The NHC-coated Au-NPs 590 were then obtained with an average size of 2.6 nm, which was the same as for the thioether stabilized Au-NPs. However, 590 was only stable for a limited period of time (ca. 12 h) in solution (DCM, DMSO, or CH3CN). It was found that the loss of NHC−Au complexes from the surface of the NPs into solution was responsible for the poor stability of 590. Interestingly, the same poor stability associated with leaching of NHC−metal species was also observed for the NHC-coated Pd-NPs prepared by the same ligand exchange method in this work. Later, with rational design of novel NHCs, Ravoo et al.308 prepared the first highly stable NHC stabilized Pd-NPs 593−594 by a ligand exchange strategy (Scheme 115). The NHC precursors 591 and 592,

deprotonation of the chiral NHC precursor 595 in the presence of presynthesized Pd-NPs at 50 °C under basic conditions in toluene.318 596 was found in sizes of 25−35 nm exhibiting magnetism and could serve as recyclable nanocatalyst for asymmetric synthesis (section 4.7). It should be noted that this synthetic protocol was also successfully applied for four other NHC precursors bearing similar structural features as 595. However, 596 showed the best catalytic performance in asymmetric α-arylation reactions, which clearly indicated the importance of the employed NHC ligand. The attachment of NHC moieties onto metal nanoparticles stands in contrast to the aforementioned, distinctly molecular structures used in the immobilization of NHC compounds. The main objective of accordingly immobilized carbenes is the stabilization of the nanoparticles, while an effect on the catalytic activity is usually only a benefit. The immobilization can proceed via two routes, either by decomposition of a molecular metal NHC complex or by ligand exchange on the NP surface. When furnished with suitable NHC ligands, the nanoparticles can be stabilized against agglomeration for several months. 2.2.5. Immobilization via Noncovalent Interactions. In addition to the heterogenization methods mentioned above, other immobilization methods with weaker interaction modes between the NHC species and the support such as electrostatic effects, adsorption, and entrapment have been reported. Although these methods are less frequently employed due to the relatively weak binding effect, they can still be applicable approaches for the immobilization of NHC compounds if suitably designed. Two advantages of these methods are usually mentioned, especially when using adsorption or entrapment methods.319 One is that a specific design or modification of the target ligand or complex may not be required, which suggests that a direct immobilization of the active species applied in homogeneous conditions is possible. Another is that many of these methods are relatively easy and effective, which

Scheme 115. Synthesis of Highly Stable Pd-NPs 593−594 through Ligand Exchange308

which bear long aliphatic chains on their backbones, were used to introduce steric repulsion between the NPs and form protective monolayers on the surface. 593−594 were synthesized by mixing bis(tetraethylene glycol monomethyl ether)sulfide functionalized Pd-NPs with the corresponding NHC precursor (591 or 592) and NaOtBu in a two phase solvent system of acetonitrile and hexane at room temperature. It should be noted that the nonpolar didodecylsulfide-stabilized Pd-NPs were not useful for this synthesis as the ligand AR


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significantly facilitates the immobilization process, therefore leading to an easy access for industrial applications. 2.2.5.1. Immobilization via Electrostatic Interaction. Immobilization via electrostatic interaction is a frequently addressed, noncovalent heterogenization method, where charged complexes or ligands are deposited on supporting materials of opposite charge by an exchange reaction.319 To prepare charged NHC compounds for immobilization, the modification of the NHC moieties with charged substituents is the most frequently used method. In some cases, other ancillary ligands coordinated to the metal center have been modified. The polyvinylpyridine (PVPy) supported NHC−Pd complex 598 was obtained by protonation of the PVPy support with HCl, followed by addition of the sulfonated NHC−Pd complex 597 in water at room temperature for 24 h (Scheme 117).193 The immobilized compound was obtained in amorphous state with ∼78% of the PVPy particles less than 100 nm and a Pd content 0.046 mmol/g.

602, useful for both batch and continuous flow reactions (Scheme 119). To synthesize 602, a solution of 601 in acetone

Scheme 117. Synthesis of Immobilized NHC Catalyst 598 by Electrostatic Grafting onto Protonated Polyvinylpyridine193

was mixed at room temperature under inert atmosphere with a presynthesized silica gel, which was functionalized by lithium ptoluenesulfonate. In order to facilitate the cationic exchange process, degassed water was also added to the reaction mixture after 1 min. The immobilized catalyst 602 was finally obtained as a dark-green powder with a loading of 0.09 mmol of Ru/g. Since the catalyst loading was higher than the typical loading (0.01 mmol/g) obtained by physisorption of silica based supports,321 electrostatic force was considered as the prevailing interaction response for this immobilization. Fernandez et al.322,323 reported the preparation of clay-supported NHC−Pd complexes via electrostatic interactions and physisorption (Scheme 120). In this study, the clay supports (bentonite or

Scheme 119. Ru Metathesis Catalyst 602 Immobilized onto Sulfonated Silica via Electrostatic Interactions320

Scheme 120. Immobilization of 603 onto Clay Compounds Bentonite and MK-10322,323

Skowerski and co-workers157−159 developed a general method to immobilize a series of Grubbs-type Ru−NHC metathesis catalysts through a strong interaction between the polar quaternary ammonium tag of the NHC ligand and surface-bound silanol group of the silica supports. In this approach, the ammonium tagged Ru−NHC complex 599 was simply added to a well-stirred silica suspension in dichloromethane at room temperature. After the reaction was completed (1−24 h), the solvent was filtered off, and the solid compound was collected and dried in a vacuum thus preparing the silica-supported Ru−NHC complex 600 (Scheme 118). Mauduit and co-workers320 reported a pyridinium-tagged Ru−NHC complex 601, which was further immobilized onto sulfonated silica to prepare the supported metathesis catalyst Scheme 118. Ammonium Tagged Ru Complex 600 Immobilized via Electrostatic Interaction157−159

MK-10) were mixed with the corresponding Pd complex 603 in dichloromethane solution and stirred at room temperature for 24 h under N2 atmosphere. The as-obtained solid compounds 604−605 had a Pd loading in the range 0.056−0.075 mmol/g. In the case of bentonite, the immobilization was considered to be caused by the electrostatic interactions between the NHC− Pd cation and the bentonite layer, while in the case of MK-10, the hydrogen bonding between the NHC−Pd cation and the hydroxyl groups on the clay surface was likely the main interaction of immobilization. AS


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2.2.5.2. Immobilization via π−π Stacking. The NHC−Ru complex 607, supported by single wall carbon nanotubes (SWCNT), was synthesized by immobilization of the pyrenetagged NHC−Ru complex 606 onto the sidewalls of the SWCNT support (Scheme 121).324 The aromatic pyrenyl

stirring at room temperature for 10 h. The as-prepared GOsupported NHC compound 610 was found with a BET surface area of 165 m2/g as well as a similar Pd and Ru content of 0.49 mmol/g. Reiser and co-workers188 prepared the magnetic-nanoparticle-supported NHC−Pd catalyst 612 through the π−π stacking interaction between the graphene layer of the Co/C nanomagnets and the pyrene units of NHC−Pd complex 611 (Scheme 123). The reaction between 611 and the Co/C nanomagnets was performed by 2 h of sonication of the reaction mixture in water combined with an interval of overnight stirring at room temperature. 612 was obtained with a Pd loading of 0.1 mmol/g and could be easily separated from the reaction mixture with the aid of an external magnet. Furthermore, it was found that the π−π stacking interaction between pyrene groups and graphene was strongly temperature dependent in polar solvents. On the basis of this feature, a “boomerang”-type catalyst (catch−release system) could be developed. In this case, the desorption of 611 from the solid support occurs at elevated reaction temperatures (e.g., 100 °C) to release the active species into the homogeneous aqueous phase, while the reimmobilization of 611 onto the nanoparticle proceeds at room temperature when the reaction is completed. Schulz et al.196 reported the immobilization of an NHC−Ru metathesis catalyst by charge-transfer interaction between anthracene and 2,4,7-trinitrofluoren-9-one (TNF). In this synthesis, the anthracenyl-tagged NHC−Ru complex (Figure 10) was mixed with a TNF-grafted silica support in a mixed solvent system of dichloromethane and hexane, in a molar ratio of 1/3, for 10 min. The as-prepared solid catalyst 613 was found with 77% of the introduced NHC−Ru complex absorbed on the silica support. It should be noted that this chargetransfer interaction is reversible, and the silica support can be recovered and reloaded with NHC−Ru complex for a new batch of catalytic reactions. 2.2.5.3. Immobilization via Physical Interaction. Jacobs et al. and Balcar et al.327,328 reported the immobilization of Ru− NHC metathesis catalysts 614 and 615 by a direct absorption method (Figure 11). The immobilization processes were carried out by simply mixing the silica material (e.g., silica gel, SBA-15) with the corresponding Ru−NHC complex in toluene solution and stirring the mixture at room temperature until the solution became clear. With respect to complex 614, the as-prepared supported catalyst exhibited a Ru loading ranging from 0.5 to 0.6 mmol/g, while in the case of 615, a slightly lower Ru loading between 0.092 and 0.097 mmol/g was observed. Leaching was detected for both cases, especially when polar solvents were used, which might indicate that these absorption methods featured relatively weak binding effects between the complex and the support. Considering the mechanism of such immobilization methods, the direct chemical interaction between the Ru center and the silanol groups of the silica was found more plausible than simple physisorption as evidenced by a clear decrease of the isolated O−H stretch of the supported compounds in IR spectra of 614. However, a fully confirmed mechanism would still require further investigations. A similar approach was performed for a series of NHC−Ru metathesis catalysts that were grafted onto commercially available silica gel supports for continuous-flow metathesis reactions.329 An evaluation of the adhesion of the different NHC−Ru complexes to the silica support as well as a systematic survey on a variety of porous silica materials (e.g., SBA-15, MCM-41, ZSM-5, and D11-10) for the immobilization

Scheme 121. Grafting of Metathesis Catalyst 606 onto Carbon Nanotubes via π−π Stacking324

group strongly interacts with the sidewalls of SWCNTs through π−π stacking, therefore providing a fixation point for complex 606.325,326 The synthesis of 607 was performed by adding 606 to a highly dispersed solution of SWCNTs in CH2Cl2 followed by sonication for 5 min before the mixture was left standing for an extra 3 h at room temperature. 607 was obtained as a dark solid with a Ru loading of 0.22 mmol/g. A desorption of complex 606 from the SWCNTs depending on the solvent as well as the temperature was observed. A significant amount of 606 desorbed in benzene, toluene, CH2Cl2, or THF, whereas only a small amount of 606 was desorbed when using ethyl acetate or acetone. Moreover, the desorbed complex could be reimmobilized onto the SWCNTs support using acetone as solvent, suggesting that the π−π stacking interaction between the pyrene moiety and the SWCNTs was actually reversible in this case. With these intriguing features, 607 was found to be recyclable and could be reloaded with complex 606 when required, thus providing a new strategy to control the immobilization process and to recycle both the catalyst and the SWCNTs. A similar approach was also reported for the coimmobilization of pyrene functionalized NHC−Pd and NHC−Ru complexes by π−π stacking interaction onto a graphene oxide (GO) support (Scheme 122).190 In this study, the NHC−Pd complex 608, the NHC−Ru complex 609, and the reduced graphene oxide were initially mixed in CH2Cl2, and the resulting suspension was sonicated for 30 min followed by Scheme 122. Synthesis of 610, Wherein the NHC Metal Complexes Are Bound by π−π Interactions190

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Scheme 123. Grafting of Pd Complex 611 onto Co/C As Described by Reiser et al.188

prepared SBA-1 encapsulated catalyst could also be applied in polar reaction conditions, while the analogue catalyst prepared by direct absorption could only be used in nonpolar reaction conditions. Furthermore, this encapsulated catalyst was found to contain 70% of the Ru complex initially added, and could be recycled seven times in ring-closing-metathesis (RCM) reactions with the use of dichloromethane as solvent. Cowley et al.333 described the preparation of an NHC−Au complex incorporated into nanofiber composites by electrospinning mixtures of the NHC−Au complex 616 or 617 (Figure 12) with aqueous solutions of poly(vinyl alcohol) (PVA). The nanofibers obtained had a length of 250−300 nm and were subsequently tested for antimicrobial activity.

Figure 10. Anthracenyl-tagged Ru−NHC complex immobilized onto TNF−silica.196

Figure 12. Gold−NHC complexes that were incorporated into nanofiber composites by electrospinning.333

2.2.5.4. Immobilization via Other Noncovalent Interactions. F−F-based binding is a type of noncovalent interaction between heavily fluorinated or perfluorinated compounds.334,335 Due to its unique features, this affinity has been extensively studied, e.g., for chemical synthesis and separation techniques.336,337 Immobilization of perfluorotagged homogeneous catalysts via F−F interaction is also a feasible method, which has been successfully applied in various studies.338−340 Cai et al.191 reported a perfluoro-tagged NHC− Pd complex, which was further immobilized onto fluorous silica gel (FSG) to prepare the supported catalyst 618 through F−F based binding (Figure 13). To synthesize 618, the perfluoro-

Figure 11. Ru complexes 614 and 615 that were absorbed onto silica.327,328

of Hoveyda−Grubbs II catalyst under continuous-flow conditions were conducted.330 Yang et al.331 also tested a series of silica materials such as silica gel, MCM-41, SBA-15, SBA-16, FDU-1, and SBA-1, to immobilize a second generation Hoveyda−Grubbs catalyst by direct absorption. In this study, the silica material was dispersed into the toluene solution of the second generation Hoveyda− Grubbs catalyst and stirred at room temperature for 6 h. The resulting solid compound was filtered off and dried in a vacuum, affording the immobilized catalyst with relative loadings ranging from 67 to 90% compared to the initially added amount of Ru complex. It was found that SBA-16 and SBA-1 had the largest adsorption capacity for the Ru complex. Furthermore, the immobilized catalyst with SBA-1 as support exhibited a significantly enhanced recyclability as compared to the others. This may be due to the isolated nanocages of SBA-1, which have a suitable size to prevent the mononuclear NHC− Ru complex from dimerization via spatial limitations. A followup work by the same group described a more thorough study on SBA-1 supported second generation Hoveyda−Grubbs catalysts.332 An additional step was conducted to reduce the window sizes of SBA-1 via silylation with dichlorodiphenylsilane to ensure the encapsulation of the NHC−Ru complex in the nanocages of the support. With this strategy, the as-

Figure 13. Immobilized Pd−NHC complex 618.191

tagged Pd complex was heated in perfluorooctane at 100 °C for 12 h followed by addition of FSG. The reaction mixture was then stirred for 2 h at 100 °C before the solvent was removed to afford 618 as a gray solid, which was found with a Pd loading of approximately 0.009 mmol/g. It should be noted that a leaching of Pd (3 ppm) was observed from the crude products during recycling experiments, which may arise from the AU


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a solid surface (e.g., Au, Si, SiO2, Al2O3) and are organized into ordered domains.344,345 Since sulfur compounds have a strong affinity to Au surfaces, the preparation of SAMs by attaching organosulfur compounds, especially alkanethiolates, to Au surfaces is the predominantly investigated procedure in this area of research.344,346 Immobilization of a metal complex on a solid surface through the formation of SAMs has been successfully applied for catalyst immobilization and thus provides an intriguing approach to obtain solid-supported compounds for various applications.347−349 Hara and co-workers350 reported the first example of a SAM supported Rh−NHC complex 627 by immobilization of an alkanethiolate terminated Rh−NHC complex onto a gold surface (Figure 14). The synthesis of 627 was conducted by

relatively weak F−F interactions between 618 and the FSG support. Meyer and co-workers341 reported the preparation of the silica-supported ionic liquid phases (SILP) 621 and 622, which were composed of ionic liquid crystals with Ni−NHC complexes dissolved therein (Scheme 124). In this synthesis, Scheme 124. Preparation of the Ni−NHC Containing SILPs 621−622341

the Ni complexes 619 and 620 were mixed with ionic liquid crystals and the porous silica support (silica-100) in dry toluene, affording the SILP materials 619 and 620 (10 wt % Ni−NHC complex) after removal of the solvent. Although the as-obtained SILP materials were not applied as supported catalysts, the strategy employed in this work can still be a potential choice for the immobilization of NHC compounds. The same strategy was also successfully performed in order to immobilize Grubbs-type catalysts as SILPs.342 Another very interesting way of immobilizing NHC complexes was recently demonstrated by Wang et al.,343 who immobilized polymeric Pd−NHC complexes 623 and 624 by coating magnetic Fe3O4-NPs with them (Scheme 125). The NPs were encapsulated in a microwave one-pot reaction in DMF, polymerizing the complexes around them. The Pd loading was found to be 1.07 and 0.82 mmol/g for 625 and 626, respectively. The synthesized particles could be separated magnetically from the reaction mixture, which made them useful catalysts in the palladium catalyzed Suzuki−Miyaura reaction. Self-assembled monolayers (SAMs) are molecular assemblies formed spontaneously by adsorption of an active surfactant on

Figure 14. Rh−NHC complex 627 immobilized onto a gold surface as SAMs.350

simply immersing a gold-coated plate into a THF solution of the Rh−NHC complex at room temperature for 20 h. In order to prepare the desired monolayer compound, a special structural design of the NHC moiety was pursued. First of all, the sulfur-terminated alkyl chain of the NHC moiety was anchored at the backbone carbon atom rather than onto the nitrogen atoms so that the metal centers would direct toward the bulk phase. Second, sterically undemanding methyl groups were used as N-substituents of the NHC moieties in order to reduce the interaction between the head groups of the monolayer. Lee et al.185 described another example of a SAM supported NHC precursor 628 (Scheme 126) via the strong

Scheme 125. Coating of Magnetic Fe3O4−NPs with Polymeric Pd−NHCs343

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immobilization process. Therefore, the reaction conditions for the metalation have to be compatible with the supporting materials. It is worth mentioning that the loading of the supported NHC precursors can influence the metalation step as well, as a low ligand loading may lead to a low metalation rate and increase the difficulty on further characterization. The synthesis of NHC−metal complexes under homogeneous conditions has been covered in several review articles and book chapters22,351−355 and will be only briefly discussed herein for some special cases of homogeneously conducted preimmobilization metalation reactions. The focus will be laid on postimmobilization metalation reactions carried out under heterogeneous conditions. In the past decades, a myriad of synthetic methods for NHC−metal complexes has been developed.352 For the reasons stated above, metalation methods for immobilized NHC precursors are required to exhibit a high tolerance toward functional groups, mild reaction conditions, and high reaction efficiency. Accordingly, basic deprotonation synthesis and transmetalation of silver complexes (silver route) are the two most frequently used metalation routes for immobilizing NHC complexes as they show good adaptability and feasibility (Scheme 127). Other metalation reactions are usually only applied for specially designed systems and are less frequently reported.

Scheme 126. Synthesis of SAMs of NHC Precursor 180 on a Gold Surface185

affinity between thiol groups and a gold surface. To prepare 628, the Au-coated plate was directly submersed into the ethanol solution of 180 at room temperature for 3 h. It is worth mentioning that this supported NHC precursor 628 can be further modified by anion exchange to prepare the supported NHC precursors with different counterions. 2.3. Metalation of NHC Precursors

A crucial step in the synthesis of immobilized NHC complexes is the metalation of the precursor compound. Major aspects concerning metalation reactions will be discussed in this section according to the applied metal and the stage at which metalation is performed (Figure 15) In the following discussion the term “homogeneous metalation” refers to the preparation of functionalized NHC complexes, which are subsequently immobilized in a second step (route I, Figure 15). The design and synthesis of such NHC complexes requires the consideration of two synthetic aspects. On the one hand, the metalation methods and their reaction conditions have to be compatible with the functional groups of the NHC precursors. For example, when working with carboxyl functionalized NHC precursors, the addition of a base for deprotonation of the C2 position can also lead to the deprotonation of the carboxyl group, thus leading to undesired products. On the other hand, the synthesized NHC complex also has to be compatible with the respective immobilization reaction. The NHC complexes require a relatively high stability for further immobilization and need to retain their catalytic activity after immobilization. Another important issue that has to be considered is the solubility of the NHC complexes, especially when using insoluble supports, as it may significantly affect the efficiency of the immobilization reaction. In contrast, heterogeneous metalation refers to metalation of supported NHC precursors, which is mostly conducted under heterogeneous conditions (route I, Figure 15). For these insoluble NHC precursors, the selection of the correct metalation method is critical and requires thorough consideration. First, mass transport can be an important issue particularly when porous materials (e.g., mesoporous silica, zeolite) or swellable polymers are used. In this sense, the metalation reaction is preferred in an efficient and straightforward manner. Second, the supporting materials should retain their main structural features after the

Scheme 127. Synthesis of NHC Complexes by Basic Deprotonation of NHC Precursors and Transmetalation of Ag−NHC Complexes

As shown in Scheme 127, the base deprotonation route, which is a widely used method for the preparation of metal NHC complexes, can usually be divided into two types of

Figure 15. Synthetic strategies for the preparation of supported NHC−metal complexes. AW


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reported methods with special considerations concerning the compatibility of the functional groups to the reaction conditions. Only a few examples report special circumstances during the syntheses. It is worth mentioning that several trialkoxysilyl functionalized NHC−Pd complexes prepared by the base route were obtained containing impurities and directly used for further immobilization,68,79,86 while most of the trialkoxysilyl functionalized NHC−Pd complexes synthesized via the silver route were usually isolated in pure form.100,101,103,108 2.3.1.2. Heterogeneous Metalation. Among the various methods for the preparation of NHC−Pd complexes in homogeneous conditions, base deprotonation is employed frequently for heterogeneous applications and appears to be the most convenient synthetic route. Lee and co-workers203 first reported the metalation of PS-supported compound 191 by using Pd(OAc)2 as well as an external base Na2CO3 in a mixture of water and DMF (1/1) for the preparation of a PSsupported NHC−Pd complex (Scheme 128). Following this

processes: (1) the deprotonation with an external base followed by metalation with a metal precursor and (2) the deprotonation with an internal base (i.e., the metal precursor). The choice between these two processes is usually dependent on the nature of the NHC precursors used. As mentioned before, this method may be of limited use for those metal or NHC precursors bearing acidic or electrophilic groups besides the C2 proton in the imidazole ring. A major advantage of this method is that the handling of free NHCs, which are usually air and moisture sensitive, can be circumvented, which facilitates the reaction workup. Furthermore, this method can be applied for a broad variety of imidazolium salts and metal precursors. The transmetalation of Ag−NHC complexes has also proved to be successful in the synthesis of a variety of metal NHC complexes. First, Ag−NHC complexes for transmetalation can easily be prepared by the reaction of imidazolium salts and basic silver compounds (e.g., Ag2O, AgOAc) under mild conditions and usually in good yields. Second, the convenient handling of Ag−NHC complexes provides an easy way to overcome the difficulties associated with other methods, e.g. handling strong bases, harsh reaction conditions, and complicated work-ups. In fact, many syntheses or transmetalation reactions of Ag−NHC complexes are conducted under aerobic conditions and even in aqueous solution for some cases. However, it should be noted that this method may not be suitable for the postimmobilization metalation with insoluble NHC precursors, as the silver reagent may also be insoluble in regular solvents, thus leading to a low efficiency in these reactions. 2.3.1. NHC−Pd Complexes. 2.3.1.1. Homogeneous Metalation. Palladium-catalyzed cross-coupling reactions, a powerful synthetic tool in both academic and industrial processes, have been widely used for the synthesis of fine chemicals, functional materials, and industrial raw products.5,6,356 Since the first demonstrated application of NHC−Pd complexes in a Mizoroki−Heck reaction reported by Herrmann et al.,357 NHCs have become powerful ancillary ligands prevailing over phosphines in palladium-catalyzed cross-coupling reactions. In this context, NHC−Pd complexes are unarguably the most intensively studied NHC complexes and have been frequently reported as immobilized catalysts. The vast majority of NHC− Pd complexes can be classified into two general types: monoNHC coordinated and bis-NHC coordinated Pd complexes. Within these two types, NHC−Pd complexes with different structural features have been reported. The synthesis of monoNHC−Pd complexes is usually achieved by both the base route and the silver route, while the preparation of bis-NHC−Pd complexes is mainly performed via the base route (Figure 16). When preparing functionalized NHC−Pd complexes for immobilization, syntheses are mostly adapted from literature-

Scheme 128. Synthesis of Immobilized Pd NHC Complexes (Refs 31, 46, 47, 54, 202, 203, 205, 213, 215, 216, 219, 221, 256, 358−361)

work, a series of PS-supported NHC−Pd compounds were prepared through this method.46,205,256,358−360 In addition to mixed solvent systems, similar to homogeneous conditions, pure solvents such as DMSO, THF, and DMF were reported more frequently for the syntheses of supported NHC−Pd complexes (refs 31, 47, 54, 202, 213, 215, 216, 219, 221, 357, 361−364). It should also be mentioned that although an external base was used in several cases to assist the deprotonation of the NHC precursors, it might not be necessary as many examples also described the successful preparation of supported NHC−Pd complexes by mere use of Pd(OAc)2. Although the use of Pd(OAc)2 as the metalation precursor appears to be the most feasible method, several aspects are worth mentioning here. First, the metalation of the supported NHC ligands was usually incomplete. For example, Lee et al.203 reported that only 15% of the NHC precursor 191 was metalated. During postmodification of the MOF-supported NHC precursor 534 with Pd(OAc)2 in THF solution, it was found that only 76% of the NHC moieties were transformed into NHC−Pd species.140 Further, the metalation of the polymeric ligand precursor 457 with Pd(OAc)2 in DMSO solution at 130 °C afforded the supported NHC−Pd compound with only a quarter of the NHC moieties coordinating to Pd.293 This can partly be attributed to the low diffusion coefficient under heterogeneous conditions. Furthermore, for polymeric supports, especially those synthe-

Figure 16. Typical coordination models of NHC−Pd complexes. AX


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sized via self-support methods, the NHC moieties are dispersed not only on the surface but also in the core, therefore inherently inhibiting the full transformation of the NHC precursors by metalation. Another reason causing low metalation ratios can be the formation of Pd-NPs during the metalation reaction. For instance, Qiao et al.95 reported the metalation of the silica supported mono-NHC precursor 287 with Pd(OAc)2 in ethanol solution at room temperature for 24 h successfully affording the respective silica supported NHC−Pd compound. However, by using its analogues with different counterions (BF4−, PF6−, NO3−), it was found that only Pd-NPs were formed rather than supported NHC−Pd compounds. This result clearly indicates that the anion of the imidazolium salt influences the final metalation product. It is also worth mentioning that the formation of Pd-NPs in this case might also be attributed to alcohol reduction, which is a frequently used methodology to prepare noble-metal nanoparticles.365 Similar problems were encountered during the metalation of the silica-supported NHC precursor 228 with PdCl2 and CsCO3 in DMF solution.239 It was found that the formation of Pd-NPs was inevitable as the base and the solvent acted as the reducing agents, which was most probably the reason for the NP formation.366−368 The strong influence of counterions on the formation of NPs during the metalation was also confirmed for PS-supported NHC precursor 195.200 In this work, 195 (Cl−) and its analogue compounds bearing different counterions (BF4−, SbF6−, TfO−, and NTf2−) were subjected to metalation using Pd(OAc)2 and tBuOK in THF solution at 50 °C for 3 h. It was found that the immobilized Pd compounds could only be prepared by the imidazolium salts with Cl− and BF4− anions, while the use of other counterions only resulted in the formation of Pd-NPs. Besides the influence brought by counterions, Ying et al.291 observed that the ratio of the Pd(OAc)2 and NHC precursors could also affect the formation of NPs during the synthesis of their COF-supported NHC−Pd complexes.291 It was observed that Pd-NPs would form when the ratio of Pd(OAc)2 to supported NHC precursor 450 was above 0.5, which indicated that a suitable amount of metal precursor was important to prevent their formation. Additionally, a low ligand loading on the support can induce NP formation, since a dispersed distribution of the ligand inhibits the formation of bis-NHC−Pd complexes by two adjacent NHC ligands.54 Second, in several studies the exact coordination geometry around the Pd centers of the final, immobilized NHC−Pd compounds is ambiguous, especially for those with mono-NHC ligands. In general, the metalation of bis-NHC ligands with Pd(OAc)2 in homogeneous conditions leads to the formation of bis-NHC−Pd complexes by one ligand, while mono-NHC ligands tend to form bis-NHC−Pd complexes by two separated NHC ligands. However, supported mono-NHC ligands exhibit a limited accessibility for the dissolved Pd precursors which may lead to the formation of unpredictable Pd structures or PdNPs rather than the designated bis-NHC−Pd complexes. Accordingly, unusual NHC−Pd structures, which had not been observed in homogeneous syntheses, have been reported. For instance, Lee and co-workers described the formation of the immobilized Pd complex 629 via the reaction of 425 and Pd(OAc)2 in DMSO solution (Scheme 129).47,360 Although the metalation procedure was adapted from a well-established literature method,362 the formation of a bis-NHC Pd complex with two weakly coordinating PF6− anions was surprising and had not yet been reported in homogeneous phase. Sen et al.102

Scheme 129. Synthesis of PF6-Coordinated Pd−NHC 62947,360

described the metalation of the silica-supported mono-NHC precursor 372 with Pd(OAc)2 in toluene at 50 °C for 8 h. The as-prepared silica-supported NHC−Pd complexes 630 and 631 were considered to have two sulfonate groups coordinating to the Pd center (Scheme 130); however, no further characterScheme 130. Preparation of the Bis-sulfonyl Bis-NHC−Pd Complexes 630 and 631102

ization was conducted to confirm this coordination environment. Several reports mention the formation of immobilized compounds with mixed forms of NHC−Pd complexes. Metalation of the mono-NHC precursor 474 with Pd(OAc)2 and KOtBu in THF solution yielded the immobilized Pd−NHC 632, which contained both Pd(0) and Pd(II) species (Scheme 131).133 Lee et al.219 described another supported NHC−Pd Scheme 131. Synthesis of a Mixed Oxidation State Pd−NHC Complex133

compound 633 obtained through the reaction between the immobilized imidazolium salt 198 and Pd(OAc)2. Due to the bulky substituents of the NHC moieties, 633 (Scheme 132) was found to contain a mixture of two mono-NHC Pd(II) species, Pd−NHC−OAcCl (major) and Pd−NHC−Cl 2 (minor), as revealed by the Pd loading and XPS analysis. Apart from Pd(OAc)2, some other metal precursors were also employed for the synthesis of immobilized NHC−Pd complexes. Metalation of the GO-supported NHC precursor AY


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Scheme 132. Mixed Coordinative Environment in an Immobilized Pd−NHC Complex219

Scheme 135. Preparation of NHC−Pd Complexes 636−641 with Various Ancillary Ligands134,135

398 by H2PdCl4 in water yielded 634 (Scheme 133).154 Luo et al.220 described the synthesis of PS-supported NHC−Pd Scheme 133. Metalation of Imidazolium Functionalized Graphene Oxide by H2PtCl4154

temperatures. However, no detailed characterization was conducted in this work to further confirm the formation of each designated NHC−Pd microstructure. Aside from the typical imidazolium precursors, Buchmeiser et al.51 reported the metalation of the NHC−CO2 adduct 418 with PdCl2. This led to the formation of the polymer-supported NHC−Pd compound 642 (Scheme 136), which was a mono-NHC Pd

Scheme 134. Silver Route Used for the Synthesis of 635

Scheme 136. Polymer-Supported NHC−Pd Compound Synthesized from CO2 Protected Carbene 41851

220

compound 635 via the silver route (Scheme 134). In this work, the polymeric NHC precursor 199 was first reacted with Ag2O to prepare the corresponding supported NHC−Ag complex, which was then used in transmetalation with Pd(OAc)2 to yield the supported NHC−Pd compound 635. Further characterization of 635 indicated that it possibly contains three different NHC species: bis-NHC−Pd, monoNHC−Pd, and mono-NHC−Ag species. Interestingly, only 77% of the silver carbene was transmetalated into a Pd carbene as revealed by the Ag (0.52 mmol/g) and Pd (1.49 mmol/g) contents of 635. A series of immobilized mono-NHC−Pd compounds with different ancillary ligands 636−641 was synthesized by adapting literature methods originally developed in homogeneous conditions (Scheme 135).134,135 In a typical synthesis, the mesoporous silica supported NHC precursor 477 was reacted with the corresponding palladium precursor (e.g., Pd(OAc)2, Pd(acac)2, Pd(allyl)Cl2) and/or the ancillary ligand in an aprotic solvent (e.g., THF, 1,4-dioxane) at elevated

species as revealed by its Pd loading. Similarly, the reaction of [IrCl(COD)]2 and [RhCl(COD)]2 with 418 afforded the corresponding supported NHC−Ir and Rh compounds. 2.3.2. NHC−Ru Complexes. Nowadays, olefin metathesis is considered a powerful synthetic tool for the formation of C− C double bonds in both organic synthesis and polymer chemistry.369,370 The discovery of ruthenium-based complexes by Grubbs et al.371 in 1992 triggered a great interest in olefin metathesis, broadening the scope of research in this field. Furthermore, the introduction of NHCs as ancillary ligands for Ru based olefin metathesis catalysts offered tremendous improvements in activity and stability compared to bisphosphine Ru catalysts.9,372 Among various NHC−Ru complexes, the mono-NHC−Ru metathesis catalysts Grubbs II and Hoveyda−Grubbs II (Figure 17) are the two most effective and widely applied catalysts. Accordingly, the immobilization of these two complexes and their analogues AZ


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in toluene solution to afford the corresponding NHC−Ru complex, which was then desilylated by HCl to finally prepare the hydroxyl functionalized NHC−Ru complex 643 for further immobilization. In contrast to hydroxyl groups, trialkoxysilyl groups are compatible with basic and nucleophilic reaction conditions; thus typical metalation conditions for Grubbs II or Hoveyda I catalysts can be applied directly to trialkoxysilyl functionalized NHC precursors. In view of this, trialkoxysilyl functionalized Ru−NHC complexes 279, 280, 333, and 497 were prepared by direct treatment of trialkoxysilyl functionalized NHC precursors 60 and 114−116 with commercialized Grubbs I or Hoveyda−Grubbs I catalysts under basic conditions (Scheme 139).63,64,98

Figure 17. Grubbs II and Hoveyda−Grubbs II catalysts.

quickly became the subject of intense research to obtain recyclable catalysts. As shown in Scheme 137, a Grubbs II catalyst can be prepared from Grubbs I via ligand exchange of one phosphine Scheme 137. Synthesis Pathways for Grubbs II and Hoveyda−Grubbs II Catalysts373

Scheme 139. Preparation of Different Trialkoxysilyl Functionalized Grubbs II and Hoveyda−Grubbs II Type Catalysts Starting from Commercially Available Catalysts63,64,98

ligand by free NHCs or NHC adducts.373 For a Hoveyda− Grubbs II type catalyst, ligand exchange of Grubbs II or Hoveyda I catalysts can both be feasible approaches. Since all these synthetic routes are simple and effective, and can be performed under mild conditions, they can also be employed directly as metalation methods for the preparation of immobilized Ru−NHC metathesis catalysts. 2.3.2.1. Homogeneous Metalation. Considering the preparation of functionalized NHC−Ru complexes in homogeneous phase, a major concern is the compatibility of functional groups of the NHC precursors with basic or nucleophilic reaction conditions. Fürstner and co-workers29,258 described the preparation of hydroxyl functionalized Grubbs II type catalyst 643 by consecutive protection and deprotection of the hydroxyl group of NHC precursor 5 during the metalation step (Scheme 138). In this synthesis, the hydroxyl group of 5 was first silylated with hexamethyldisilazane. The protected ligand was then reacted with a Grubbs I catalyst in the presence of KOtBu

2.3.2.2. Heterogeneous Metalation. With respect to Grubbs II type Ru catalysts, direct metalation of supported NHC precursors with Grubbs I in the presence of an external base is the most frequently used immobilization strategy. In an early example Blechert et al.223 described the direct metalation of the PS-supported NHC precursor 212 with Grubbs I complex after treatment with KOtBu in THF solution (Scheme 140). The supported Ru−NHC complex 644 was obtained with loading levels ranging from 0.14 to 0.40 mmol/g, depending on the initial loading of the supported NHC precursor used (0.50− 0.90 mmol/g). The same synthetic strategy was employed in following reports preparing supported NHC−Ru complexes of Grubbs II type.36,37,50,78,187,252 The Ru loading of these

Scheme 138. Preparation of a Hydroxyl Functionalized Grubbs II Catalyst through Protections and Deprotection of the Hydroxyl Group29,258

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Scheme 140. Immobilization of a Grubbs I Catalyst onto NHC Functionalized PS223

Scheme 142. Immobilization of a Grubbs II Type Ru−NHC Complex via a Polymer Bound Pyridine Moiety380

supported catalysts lay between 0.004 and 0.175 mmol/g. In most of these syntheses, an excess amount of Ru complex was employed and mixed directly with the reaction suspension, in which the supported NHC precursors were pretreated with base (e.g., NaH, NaOtBu, KOtBu, and KHMDS). Regarding the immobilization of Hoveyda−Grubbs II type Ru complexes, the most representative method is to react Grubbs I with supported benzylidene ligands rather than supported NHC ligands. Therefore, immobilization is realized by a ligand exchange process rather than metalation of the NHC ligand. Binding the Hoveyda−Grubbs II complex via the benzylidene ligand allows a release−return mechanism, which facilitates the recovery of the Ru catalyst from the reaction mixture (“boomerang effect”, see section 4.3).374 Furthermore, modification of the benzylidene ligand is synthetically less challenging while at the same time keeping the NHC moiety unchanged.16 Blechert and co-workers375 initially described the reaction of a polymer-supported benzylidene ligand with Grubbs II catalyst and CuCl as a phosphine scavenger, preparing a PEGA supported Ru−NHC catalyst for olefin metathesis reactions (general approach see Scheme 141). Since

Extending the ligand exchange strategy, Buchmeiser et al.382−386 reported the replacement of halide ligands of Ru− NHC metathesis catalysts with polymer-supported carboxylate ligands. As shown in Scheme 144, the polymer supported Ru− NHC catalysts 647−651 were prepared according to a general procedure, in which the supported silver carboxylate was simply mixed and stirred with Grubbs II or Hoveyda−Grubbs II type precursors in suspension. Interestingly, further addition of silver trifluoroacetate to the reaction mixture would replace both chlorine ligands of the supported NHC−Ru complexes to synthesize halogen-free catalysts, which showed increased initiation rates in metathesis reactions compared to their halogen-bearing analogues.385 Although postimmobilization metalation strategies for Ru− NHC metathesis catalysts are usually directly adapted from the analogous homogeneous syntheses, the reaction compatibility also has to be considered, especially with regard to the stability of the Ru−NHC compounds during the metalation process. As an example, Buchmeiser and co-workers36 reported the use of the organic base 4-dimethylaminopyridine (DMAP) to deprotonate supported NHC compound 405 in DCM solution. However, the Ru precursor used for the consecutive metalation step was sensitive to DMAP, which required the removal of the excess DMAP before adding the Ru precursor. Moreover, pretreatment of the supported NHC compound 212 by endcapping the remaining benzyl chloride groups of the Merrifield resin with TMSOTf (Me3SiOSO2CF3) was required, as they may react with the reaction intermediate that was generated during the metalation step.223 The same group also reported the pretreatment of a silica support with dimethoxydimethylsilane before metalation, preventing undesired side reactions between free surface Si−OH groups and the Ru−NHC complex.387 2.3.3. Coinage Metal NHC Complexes. Coinage metal NHC complexes have been intensively investigated throughout the past decades for their numerous applications and diverse structural properties.355,388,389 Ag−NHC complexes, for example, have been reported for a variety of applications such as NHC metal-transfer reagents, luminescent materials, and homogeneous catalysts. Over the past several years, the respective Au−NHCs have also achieved great successes in catalysis as well as in luminescent chemosensors.10,11,390,391 Furthermore, the Ag− and Au−NHC complexes have attracted much interest in medicinal applications due to their easy modification and high physiological stability.7,392,393 Additionally, the investigation of Cu−NHC complexes has recently emerged as a burgeoning research field, due to their potentially high catalytic performance as well as the relatively low cost of copper.390,394−396

Scheme 141. Preparation of Immobilized Hoveyda−Grubbs II Type Catalysts376−379

then a number of such immobilized Hoveyda−Grubbs II type Ru complexes synthesized by the same strategy have been reported.376−379 Another possible heterogeneous metalation strategy was presented by Kirschning and co-workers,380 who described the synthesis of the polymer supported Ru−NHC complex 645 by exchanging the pyridine ligand of a modified Grubbs II type catalyst with a polyvinyl bound pyridine (Scheme 142). Since Ru−NHC based metathesis catalysts are also applied for polymerization reactions, Blechert et al.381 reported the autoimmobilization of a Grubbs II catalyst to form the polymer-supported Hoveyda−Grubbs II type catalyst 646. This combined support preparation and immobilization of the ruthenium moiety into a one-pot reaction. As shown in Scheme 143, the benzylidene functionalized oxanorbornene monomer was first copolymerized with another oxanorbornene derivative in the presence of a Grubbs II catalyst. Further addition of CuCl to the reaction mixture afforded the polymer-supported Ru−NHC compound 646 with a Ru loading around 0.09 mmol/g. BB


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Scheme 143. Autoimmobilization of a Grubbs II Catalyst into a Polymeric Support via Ring Opening Metathesis Polymerization381

Scheme 144. Immobilization of Ru Metathesis Catalysts via Polymer Bound Carboxylate Ligands382−386

Scheme 145. Application of Various Silver Precursors in the Synthesis of Immobilized Ag−NHCs211,230,289

Since stable and easily prepared NHC complexes are preferred for immobilization reactions, Ag(I)−, Cu(I)−, and Au(I)−NHC complexes, especially the [M(NHC)(halide)]type complexes, represent the majority of immobilized coinagemetal NHC complexes, compared to Cu(II)− and Au(III)− NHC species. Among various synthetic routes for coinagemetal NHC complexes,355 the in situ deprotonation by a base and the silver transmetalation route are the two major methods to prepare immobilized Cu(I)− and Au(I)−NHC complexes, while the immobilization of Ag(I)−NHC complexes is usually accomplished by direct reaction with a silver precursor. 2.3.3.1. Homogeneous Metalation. A key issue for the preparation of functionalized coinage metal NHC complexes under homogeneous conditions is, again, the compatibility of the functional groups of the NHC precursors with the metalation reaction conditions. In most published examples to date literature reported methods were directly adapted without any special modification of the reaction conditions.136,180,181,220 Furthermore, trialkoxysilyl as well as alkenyl groups are found to be compatible with basic reaction conditions, including the use of NaOtBu.104,279 Moreover, trialkoxysilyl groups also tolerate silver metalation conditions, i.e. the use of Ag2O.124−126,265 2.3.3.2. Heterogeneous Metalation. For the synthesis of supported Ag−NHC complexes by heterogeneous metalation reactions, a variety of metal precursors can be used. Qi et al.211 described the reaction of Ag2O and the PS-supported NHC precursor 193 for the preparation of the supported NHC−Ag compound 652 (Scheme 145). Thieuleux and co-workers,230 on the other hand, used AgOC(CF3)3 as the silver reagent to prepare the silica-supported NHC−Ag compounds 653 and 654 by metalation of the meso-silica supported NHC precursors 218 and 219 (Scheme 145). Furthermore, 655 was synthesized by reaction of COF-supported NHC precursor 450 with AgNO3 in DMSO (Scheme 145).289 However, it

should be noted that 655 mainly contained Ag-NPs (3−5 nm) dispersed in the materials as revealed by TEM analysis. Following the classical silver transmetalation route, Wright and co-workers used Ag2O to metalate the ZrP-supported NHC precursor 183 followed by in situ transmetalation with AuCl(tht), preparing the immobilized NHC−Au compound 656 (Scheme 146).187 Scheme 146. Preparation of 656 via the Silver Transmetalation Route187

BC


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In addition to NHC−Cu(I) complexes, Wang et al.227 and Shukla et al.212 also reported the preparation of supported NHC−Cu(II) compounds (667 and 668, Scheme 150). By

Supported Cu(I)−NHC complexes are mainly prepared by one-pot reactions in the presence of a strong base and a copper precursor in dry aprotic solvent. For instance, in the syntheses of supported NHC−Cu(I) iodide compounds 657−662, NaOtBu served as a base and CuI as metal precursor in dry THF solution at room temperature (Scheme 147).43,87,226−228

Scheme 150. Synthesis of Immobilized Cu(II)−NHC Complexes with Different Coordination Geometries212,227

Scheme 147. Synthesis of Immobilized Copper NHC Complexes by Reaction of CuI with NaOtBu and an NHC Precursor43,87,226−228

The polymer-supported NHC−Cu(I) bromide compounds 663 and 664 were prepared by metalation of NHC precursors 406 and 407 with soluble CuBr·SMe2, in the presence of NaOtBu as base (Scheme 148).41 Similarly the hyper-cross-

using Cu(OAc)2 as the metal precursor, 667 was obtained as a mono-NHC−Cu(II) complex, which was later on successfully applied as catalyst in the oxidative coupling of terminal alkynes and H-phosphonates. In contrast, 668 was obtained as a bisNHC−Cu(II) compound using CuCl2·H2O. It is worth mentioning that the synthesis of mono-NHC−Cu(II) species similar to 667 has been reported in homogeneous phase,398 while to the best of our knowledge no such structures have been described for the bis-NHC−Cu(II) species of 668. Although the synthesis of NHC coinage-metal complexes in heterogeneous conditions can be easily adapted from homogeneous syntheses, several aspects require consideration. First, the tolerance of the supporting materials toward the metalation reaction conditions has to be taken into account, especially when strong bases are used. Pourjavadi et al.,87 for example, noted that the hydroxyl groups on the surface of the support of the cellulose-immobilized NHC−Cu(I) compound 662 might consume the strong base employed for the deprotonation of the NHC precursor, thus leading to a low metal loading. Second, undissolved metal precursors (e.g., Ag2O, Cu2O) or side products (e.g., AgCl from transmetalation, metal NPs) can lead to a difficult purification process of the final, supported NHC compound. Sumby and co-workers143 found that when Cu2O was used for synthesizing 530, the separation of the desired MOF compound from the reaction residue was impeded since it was contaminated with unreacted, insoluble Cu2O. 2.3.4. Group 9 Metal (Rh, Ir) NHC Complexes. Since NHC−Rh and −Ir complexes are highly effective catalysts for various important organic transformations, e.g. hydrogenation, hydrosilylation, and hydroformylation reactions,6 the preparation of their supported analogues as recoverable and recyclable catalysts has often been investigated. The syntheses for Rh− and Ir−NHC complexes are similar, and are mainly accomplished by the deprotonation with a base in the presence of a suitable metal precursor or the silver transmetalation route. 2.3.4.1. Homogeneous Metalation. Under homogeneous conditions, the preparation of trialkoxysilyl functionalized NHC−Rh or −Ir complexes has been reported for many cases and can be achieved by both synthetic routes that are directly adapted from those for nonfunctionalized complexes. [MCl(COD)]2 type Rh and Ir precursors are most frequently employed in silver transmetalation syntheses,97,101,115,124,126 while [Rh(COD)(μ-OMe)]2 has been used as a metal source and internal base for the direct deprotonation of NHC

Scheme 148. Preparation of Supported Cu(I)−NHC Complexes from Soluble CuBr·SMe241

linked polymer supported NHC precursor 466 was metalated by CuCl in the presence of NaOtBu.397 [Cu(CH3CN)4]PF6 has also been used as Cu precursor to synthesize the MOFsupported NHC−Cu compound 530 and the carbon-supported NHC−Cu compounds 665 and 666 (Scheme 149).143,148 In Scheme 149. Synthesis of 665 and 666 from [Cu(CH3CN)4]PF6143,148

the case of 665 and 666, the corresponding carbon-supported NHC precursor was mixed with [Cu(CH3CN)4]PF6 and KOtBu in a mixture of DMF and THF (1/1) at room temperature for 48 h. As discussed earlier, Son and co-workers reported two cases of MOFs bearing NHC−Cu(I) (526 and 527) using Cu(NO 3 ) 2 and Cu 2 O as the metalation precursors.137,305 BD


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precursors. 65,115 In some cases [Rh(CO) 2 Cl] 2 266 and [Cp*IrCl2]2113,186 were also reported as possible metal precursors for the synthesis of trialkoxysilyl functionalized NHC−Rh or −Ir complexes, respectively. In a rather unusual synthesis Ö zdemir et al.264 used trialkoxysilyl functionalized tetraaminoethene to directly react with [RhCl(COD)]2 affording NHC−Rh COD complex 669 (Scheme 151).

supported NHC−Ir complex 679 (680) from [Cp*IrCl2]2 and 653 (654)-type Ag−NHC (short rigid linker to the NHC moiety).230,232,234 Using a more flexible linker to the NHC moiety and [IrCl(COD)]2, the oxygen-stabilized silica supported NHC−Ir compound 681 was obtained (Scheme 154).235 Scheme 154. Preparation of Immobilized Ir−NHC Compounds 679−681 Displaying Different Coordination Geometries Depending on the Linker230,232,234,235

Scheme 151. Application of Trialkoxysilyl Functionalized Tetraaminoethene for Immobilizing a Rh−NHCComplex264

2.3.4.2. Heterogeneous Metalation. With regard to the synthesis of supported Rh− and Ir−NHC complexes under heterogeneous conditions, the deprotonation of the NHC precursor by a base in the presence of a metal precursor appears to be the most widely used method. To prepare the PSsupported NHC−Rh complexes 670 and 671, KOtBu and [RhCl(COD)]2 were reacted with the corresponding NHC precursor in THF solution (Scheme 152).149,218 On the other

2.3.5. Miscellaneous Metal−NHC Complexes. Compared to the widely employed group 10 counterpart palladium, NHC−nickel complexes have been studied less frequently. Nevertheless, due to the lower costs of nickel compared to palladium and the potential catalytic applications including C− C cross-coupling reactions, dehalogenation, and amination, a number of NHC−Ni complexes have been investigated in the past decade.6,399 Thus, the immobilization of NHC−Ni complexes emerges as a relatively new field for further investigation. Chetcuti et al.109 described the preparation of the trialkoxysilyl functionalized NHC−Ni complex 371 by direct treatment of the NHC precursor 70 with nickelocene (Scheme 155). The product was isolated by column

Scheme 152. Metalation of Immobilized NHC Precursors with [Rh(COD)Cl]2149,218

Scheme 155. Synthesis of the Triethoxysilyl Functionalized Ni−NHC Complex 371109

hand [Ir(COD)(μ-OMe)]2 could be used as an internal base to directly deprotonate the carbon-supported NHC precursors 264−267, 195, and 209 in THF (Scheme 153), preparing the supported NHC−Ir compounds 672−678.26,28,250,260 Similarly, [Rh(COD)(μ-OMe)]2 has been used to synthesize PSsupported Rh−NHC complexes 675 and 676 starting from precursors 195 and 209.214 Alternatively, the silver transmetalation approach was applied for the synthesis of silica Scheme 153. Preparation of Immobilized Rh− and Ir−NHC Complexes Using a Bridging Methoxylate Ligand as Internal Base26,28,214,250,260

chromatography and obtained as a violet oil. Lee and coworkers238 prepared the MNP-supported NHC−Ni compounds 682 and 683 by mixing the corresponding MNP supported NHC precursors 226 and 227 with Ni(acac)2 and KOtBu in DMSO (Scheme 156). The Ni loadings of 682 and 683 were found to be 0.40 and 0.26 mmol/g, respectively. Similar to NHC−Ni complexes, the chemistry of NHC−Fe complexes has also proven to be a burgeoning research field in recent years.400 However, the development of immobilized NHC−Fe complexes is far behind. Lee et al.210 reported the preparation of PS-supported NHC−Fe compounds 684 and 685 by the reactions between the PS-supported NHC precursor 193 and iron chlorides (FeCl2·4H2O or FeCl3· 6H2O) in the presence of KOtBu (Scheme 157). It is worth BE


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ization of the support, which will be presented in sections 3.1 and 3.2. Section 3.3 will deal with the characterization of the complete catalyst, consisting of support and active site, both before and after catalysis.

Scheme 156. Preparation of MNP Immobilized Ni−NHC Complexes According to Lee et al.238

3.1. Characterization of Supported NHC Moieties

The characterization of the NHC moiety on a support basically comprises two different aspects. One is the identification of the NHC moiety within the immobilized compounds; the other is the assessment of the loading of the supported NHC. In order to confirm the formation or fixation of the desired NHC moiety after immobilization, a common strategy is to compare the analytic data of the immobilized compound with its homogeneous precursor or analogues. Various analytical tools such as NMR or IR spectroscopy are useful characterization methods for such purposes. With respect to NMR spectroscopy, a large number of publications has been published that assess NHC compounds in homogeneous condition by detailed NMR measurements. The C2 atom of NHC compounds is an excellent diagnostic parameter for NMR spectroscopy as it allows direct and convenient identification of the NHC moiety and several papers concerning this subject have been reported.401−406 This strategy can also be applied to immobilized compounds. In general, the disappearance of the signal attributed to the acidic imidazolium proton of the C2 atom in 1H NMR as well as the downfield chemical shift of the C2 atom in the 13C NMR spectrum indicates the formation of NHC compounds from their imidazolium precursor. Moreover, the substituents on the NHC compounds or their precursors can also provide characteristic signals in NMR spectroscopy. For instance, the observation of the proton signals attributed to the tert-butyl group of the supported NHC compound 548 is clear evidence to verify the successful immobilization of 546 on a Ru-NP surface.310 Further, in the 13C CPMAS NMR spectra of the meso-silica supported NHC precursor 477, the signals at 24− 30 ppm could be assigned to the isopropyl groups and were in agreement with the corresponding signals of the precursor 113 in liquid phase, which confirmed the retention of the structure after the sol−gel immobilization process.134 Concerning the immobilization of entire NHC−metal complexes, the NMR resonance of other ligands coordinated to the metal center can also cause characteristic signals, which allow identification and confirmation of the presence of the desired compound. For example, the presence of the silica-supported NHC−Ir complex 365 was confirmed by 13C NMR signals at 8 and 92 ppm, which were ascribed to the Cp* ligand coordinating to the central metal atom. Moreover, by this means the retention of the coordination environment of the precursor complex 328 on the Ir center after grafting on a silica surface was confirmed.113 On the contrary, the displacement of a COD ligand from a silica grafted Ir complex by surface oxygen was proven by 13C MAS and 1H−13C HECTOR NMR experiments.235 A similar coordination of surface oxygen functionalities was also reported for a silica immobilized NHC substituted tungsten metathesis catalyst.407 The polymer supported NHC−Ru catalyst 647 was analyzed by 31P-MAS NMR spectroscopy and showed a phosphine signal at 41.1 ppm, which nearly matched the signal of its precursor complex (Grubbs II catalyst, 41.2 ppm), indicating that no fundamental changes such as disassociation of the NHC ligand on the Ru center were observed during formation of 647.382 Additionally, the resonance signals of the counterions (e.g., PF6−, BF4−) of imidazolium salt precursors

Scheme 157. Synthesis of Immobilized Fe−NHC Complexes210

mentioning that also other metal precursors such as SnCl4, CrCl2, and AlCl3 were used to prepare corresponding supported NHC−metal compounds under the same reaction conditions. Furthermore, the synthesis of cobalt−NHC complexes from immobilized imidazolium salts can be achieved using the metal chloride as precursor as recently demonstrated in the preparation of 687 from 686 (Scheme 158).254 Scheme 158. Metalation of 686 with CoCl2254

Considering the metalation of immobilized NHC precursors, it can be said that the reaction conditions closely resemble those for homogeneous metalation. Usually the base deprotonation route is the method of choice, followed by transmetalation. For basic metal precursors such as Pd(OAc)2 or Cu(OAc), the use of an additional base can be omitted since the internal base usually suffices. Depending on the NHC functionality, loading, and distribution in the support, bis- or mono-NHC complexes are formed. Due to the limited accessibility of the NHCs, unusual coordination modes can be observed. In some cases, such as ruthenium NHC complexes, the metalation and immobilization step can be combined if, e.g., norbornene functionalized benzylidene compounds are used. An important aspect in the reaction planning process has to be compatibility of functional groups with the reaction conditions. It has to be kept in mind not only that functional sites at the NHC moiety can react with other constituents but also that the support material can interfere under reaction conditions.

3. CHARACTERIZATION OF IMMOBILIZED NHC COMPOUNDS Immobilized homogeneous catalysts in general can be viewed as a combination of two separate species: the active (organic or organometallic) moiety and the supporting (organic or inorganic) material. In this sense, the characterization of immobilized NHC compounds may be divided into two aspects, the analysis of the NHC moiety and the characterBF


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NHC moiety) of the precursor NHC−Cu complex was maintained upon immobilization. Concerning the loading of an immobilized NHC compound, there are two different aspects that require consideration: first, the amount of NHC moieties on the support, and second, the extent of metal occupation of the carbene sites. The main tool for the determination of the NHC loading of a support is elemental analysis (EA), which can provide accurate elemental contents of the overall material. Using the nitrogen content obtained from EA, the NHC loading can be calculated in the case that all nitrogen sources are defined. It is worth mentioning that TGA28,92,94,103,114 and XPS135 have also been reported as tools to evaluate the loading of NHC moieties according to the weight loss at a certain temperature or by the nitrogen content on the material surface, respectively. However, the accuracy of TGA and the accuracy of XPS are dubious, since the observed signals cannot definitely be attributed to NHC compounds on the support. Nevertheless, these two techniques might still serve as supplementary methods to correlate with the results obtained from EA, thus ensuring a more reliable determination of the loading. The loading of NHC−metal complexes on the support is usually calculated from the metal contents of the resulting material, which can be measured by atomic absorption spectroscopy (AAS/FAAS/ GFAAS), inductively coupled plasma atomic/optical emission spectroscopy (ICP-AES/OES) or inductively coupled plasma mass spectrometry (ICP-MS). The selection of the used technique mainly depends on the available equipment as all these methods are capable of conducting such determinations. Nevertheless, ICP-AES is the most frequently applied technique as it has been widely accepted as an effective and versatile spectroscopic instrument for the analysis of metals. It should be noted that the different techniques tolerate different levels of total dissolved solids (TDS); therefore, the pretreatment of the sample before analysis as well as the selection of the technique according to TDS level have to be considered. There are several reports that provide a detailed treatment of the supported NHC compounds by AAS,119,136,212 ICPAES,41,413−415 or ICP-MS,28,63,181,190,413 which can be useful guidance for conducting such analyses. The same three techniques are also reported for determination of the metal leaching of the supported NHC compounds during catalysis. Since ICP-MS provides the best detection limits (1−10 ppt) compared to the others (ICP-AES, 1−10 ppb; AAS, subppb −1 ppb), it can be regarded as a preferred tool for this analysis, while AAS especially the FAAS (sub parts per million) is not recommended. It should be noted that in some publications energy-dispersive X-ray spectroscopy (EDX or EDS) analysis is also employed to determine the loading of an NHC metal complex.42,113,221,251 However, the accuracy of this method is debatable as the NHC moieties are not always well-dispersed over the supported material.

may also serve as an indirect proof for the successful immobilization of the NHC compounds. It is worth mentioning that, due to the weak intensity of its NMR resonance, the C2 atom in some cases has not been observed, especially in solid-state measurements. In view of this, NHC precursors, which are 13C-enriched at the C2 position, were employed for immobilization experiments in order to demonstrate the accessibility of the designated process by 13C NMR spectroscopy.310 For instance, since the C2 resonance of NP-supported NHC compound 548 was not detected in solidstate 13C MAS NMR, 546 was labeled with 13C at the C2 atom. The resulting product was used to prepare the corresponding Ru-NP supported NHC compound, which showed a broad peak centered around 190 ppm in the solid-state 13C MAS NMR spectrum that was ascribed to the coordinated carbene carbon atom.310 This provided direct proof of the binding of the NHC ligand to the surface of the Ru-NPs. In addition to NMR spectroscopy, IR spectroscopy is another feasible and widely used analytic tool for immobilized NHC compounds especially in solid state. With respect to NHC precursors, namely imidazolium salts, two frequently mentioned absorption bands range between 1000 and 1200 cm−1 (near 1150 cm−1) and 1400−1600 cm−1 (near 1550 cm−1). These can be ascribed to the C2−H bond bending and the imidazolium ring CC stretching vibration, respectively, and are characteristic peaks of imidazolium salts.408−411 However, with regard to free NHCs and NHC− metal complexes, no detailed IR investigations have been published yet (except for the determination of Tolman electronic parameter (TEP) values406,412). Nevertheless, the absorption band originating from CC stretching modes near 1600 cm−1 is a frequently mentioned characteristic signal, which may suggest the presence of an NHC backbone.46,47,79,94,96,106,115,124,127,279 Moreover, similar to the NMR analysis, the particular IR absorption bands of the substituents on the NHC moiety as well as the cocoordinating ligands can induce characteristic signals, which are useful to verify the presence of the NHC species on the support. The IR absorption band of the carbonyl group (CO) of metal complex 309, for example, was also observed in the IR spectrum of supported Ru−NHC compound 335 (with only a slight shift from 1938 to 1942 cm−1), suggesting the retention of the coordination geometry at the Ru center after immobilization.127 Other absorption bands of imidazolium salts can also serve as characteristic signals, but require more detailed analysis from case to case. Again, the specific IR absorption of counterions of imidazolium salts may be an indirect proof for a successful immobilization. For 457 it was shown that the IR absorption at 840 cm−1 indicated the successful introduction of PF6− by anion exchange into a polymeric support matrix.293 In comparison to NMR and IR analyses, other spectroscopic methods such as UV/vis or XPS are less frequently employed but can also provide evidence for the immobilization of an NHC moiety. For instance, by comparison of the DRUV spectra before and after immobilization, Iglesias and coworkers106,124,126,127,129 verified the unchanged geometry and electronic surrounding of NHC compounds in a series of works and thus provided indirect proof of the retention of the NHC structure even after heterogenization. Yang and Rioux279 reported the use of XPS analysis to confirm the unchanged oxidation state of the Cu atom in the supported complex 411, which may indicate that the coordination environment (i.e., the

3.2. Characterization of Supporting Materials

The specific features of the supporting materials such as solubility, shape, size, and porosity can significantly influence the catalytic performance as well as the means of application and recovery of the immobilized compounds. To characterize these features, different techniques are required which may vary from material to material. In view of that, the different supporting materials for immobilized NHC compounds can be divided into two broad categories: soluble and insoluble BG


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Furthermore, the existence of T bands (T1, T2, and T3) ranging from δ = −49 ppm to δ = −75 ppm suggests the presence of Si−C linkages, which are typically resulting from the hydrolysis and condensation of trialkoxysilyl groups, thus confirming the bonding of the NHC moiety to the support.40,105,107,112,121,133 Additionally, the type and ratio of Si resonances can provide further hints concerning the immobilization. Ritleng et al.112 found strong T2 and T3 bands in the 29Si NMR spectrum of 478, which suggests that the NHC moieties are bound to the silica matrix mainly by two and three Si−O bonds. The observation of Q bands by Yang and co-workers133 in the 29Si NMR spectra of organosilane NHC ligand 475 indicated that a portion of the Si−C bonds had decomposed. Hesemann et al.132 rated the NHC amount incorporated into the silica matrix of 112 according to the Tn/Qn ratio. Further, Thieuleux and coworkers230 noticed two main signals in the NMR spectra of 219 associated with Q3 and Q4 substructures revealing the high degree of condensation of the silica material. In addition to its major application for identification of the NHC moiety, IR spectroscopy can also provide useful information regarding the supporting material. It allows the analysis of specific functional groups attached to the supporting materials, therefore providing clues of the immobilization success. For instance, the absence of the characteristic absorption band originating from the C−Cl bond at 1264 cm−1 in supported NHC precursors indicates the full conversion of the benzyl chloride groups on the surface of the PS resins.211,220,221 Further, Iglesias et al.129 observed a strong absorption around 3200−3700 cm−1 ascribed to Si−OH in the supported Ru−NHC compound 306, suggesting that the surface silanol groups were only partially transformed during the grafting reaction. On the other hand, Yang and Rioux279 described the disappearance of the S−H absorption band at 2580 cm−1 in SBA-15 supported NHC−Cu complex 411, indicating the grafting of the NHC−Cu complex on the surface. To obtain information regarding the shape, size, and morphology of the solid materials, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are typically used. Additionally, TEM (including STEM28,292) can be used to evaluate the formation, distribution, and aggregation of NPs inside the material. For instance, Wang and co-workers154 reported the TEM images of 634, which clearly showed well-dispersed Pd-NPs on a graphene oxide support. Yang et al.134 compared the TEM images of the silica supported NHC−Pd complex 636 before and after catalytic reaction, and found Pd-NPs were formed after one catalytic cycle. In many cases, EDX/EDS or its related mapping analysis is employed together with SEM or TEM to analyze the elemental composition of the immobilized compounds, mostly, to reveal the presence, content, and distribution of the metal within the material. For the SBA-15 supported NHC compound 368 highresolution TEM with simultaneous EDX analysis was employed to confirm the presence of Ru inside the pore channels.98 Son and co-workers290 described the use of SEM−EDX elemental mapping to reveal the homogeneous distribution of the metal centers (Ag, Cu, Pd) on the surface of the supported NHC compounds, which was synthesized from 449. Ritleng et al.112 used the same technique to analyze the distribution of Si, O, C, and N within mesoporous-silica-supported NHC compound 478, indicating that the NHC precursors were well-distributed all over the material. Furthermore, in a few examples fast Fourier transformation (FFT) processing of HR-TEM images

supports. The following section will be organized according to these two material types. 3.2.1. Characterization of Soluble Supporting Materials. Soluble supporting materials employed for NHC compounds mainly comprise organic polymers such as poly(ethylene glycol) (PEG), polyoxazolines, poly(norbornene), and polyisobutylene (PIB). Their characterization proceeds similarly to that of other organic compounds, and they are usually analyzed by liquid NMR, IR, and mass spectroscopies (e.g., ESI-HRMS, MALDI-TOF-MS182,416) as well as EA. Furthermore, gel permeation chromatography (GPC) is typically used to measure the polymer’s polydispersity index (PDI) and molecular weight (Mw), to provide useful information about the polymer properties.45 Additionally, solubility in different solvents is crucial information, especially for those immobilized catalysts that are recoverable by solvent precipitation. Bergbreiter et al.181 reported the determination of the selective solubility of PIB supported NHC complexes in different solvents by means of ICP-MS and UV/vis, which were used to analyze the metal content in solution. It should be noted that some coordination polymers,161,165,167 covalent polymers,59 NPs,151,309,310,417 and CNTs28 bearing NHC compounds are also reported to be soluble or well-dispersed in solution and can hence be analyzed by liquid NMR as well. 3.2.2. Characterization of Insoluble Supporting Materials. Regarding insoluble supporting materials, various analytic tools can be commonly applied, although the characterization methods are slightly different from material to material. Solid-state NMR analysis (13C and 29Si) is one of the most frequently reported analytic tools to characterize insoluble supported NHC compounds. With respect to inorganic supports, e.g. silica or NPs, the information obtained from solid-state 13C NMR studies mainly refers to the NHC moiety, while for organically based materials such as organic polymers, solid-state 13C NMR studies can also provide direct information to confirm the formation or stability of the supports by simple comparison of the NMR spectra before and after immobilization. It should be noted that not all the signals of carbon atoms can be detected or well-assigned in the solid-state 13C NMR spectra of supported NHC compounds, and some examples even describe that no specific signals of the NHC moiety are observed.35,47,64,200,208,214 This can be due to the following two reasons: first, solid-state NMR spectra usually exhibit a lower resolution and broader signals compared to spectra obtained in solution. This can be attributed to anisotropy effects or orientation-dependent interactions.418 Second, the NHC content in most of the supported compounds (except for self-supported NHC compounds) is much lower than that of the supporting material, with the result that the intensive resonance of the supporting material may cover or suppress the resonance of the NHC species.35,64,101,124,231 In addition to 13C NMR analysis, 29Si NMR studies are another widely used diagnostic method for the characterization of silica-based materials.419−423 29Si NMR can provide structural information not only about the supporting material but also about the immobilized NHC compounds by analysis of silicon series (e.g., Tn = RSi(OSi)n(OH)3−n and Qn = Si(OSi)n(OH)4−n) present in 29Si NMR spectra. Tetraethyl orthosilicate (TEOS) is widely used as a silica source to prepare supporting materials for NHC compounds, and in many cases the observation of Q bands (Q2, Q3, and Q4) ranging from δ = −90 ppm to δ = −120 ppm corresponds to those of condensed TEOS.64,96,101,108,132−134 BH


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PXRD pattern of the silica-supported NHC compound 636, indicating that this silica material obtained by sol−gel process possessed an ordered structure (SBA-16 type). Li and coworkers, on the other hand, used PXRD analysis to confirm the amorphous polymeric structure of supported NHC compound 462 and could rule out the presence of Au-NPs.136 The PXRD pattern of silica-supported NHC compound synthesized from ligand 228 and PdCl2 revealed the presence of Pd(0)-NPs by the presence of characteristic reflexes ascribed to the (111), (200), (220), and (311) crystallographic planes of Pd(0) nanoparticles.239 Similarly, Wang et al.154 observed the characteristic XRD reflexes for Pd(0)-NPs in their GO supported compound, which was prepared by reduction of 634 with Vitamin C. Nitrogen adsorption−desorption isotherm measurements, mainly using the BET method, are commonly used to determine the surface area and pore volume, size, and shape of solid (porous) materials. In many cases a decreased surface area was observed for the supporting material upon immobilization of NHC compounds.96,115,129 In addition to those typical characterization methods mentioned above, some other analytic tools are also employed but are usually limited to specific examples. Single-crystal X-ray diffraction (SCXRD) can be used for a precise characterization of MOF-based NHC compounds.137,140−144,305 Small-angle Xray scattering (SAXS) is applied to confirm the long-range ordering of supported NHC compounds.113,118,309 In a few cases Raman spectroscopy was also reported as an additional or alternative method to IR spectroscopy.28,86,214 Atomic force microscopy (AFM) has been used to investigate the size and distribution of the NPs formed during immobilization as well as for measuring the height of GO sheets.190,239 By confocal laser scanning microscopy (CLSM) and imaging of the absorption of a fluorescent dye, the location of imidazolium groups on the surface of PS could be observed.46,47 Vibrating sample magnetometer (VSM) measurements allow the determination of the magnetic properties of MNP supports,201 and the size distribution of NHC bearing polymer aggregates in solution can be identified by dynamic light scattering (DLS).182 Generally, it should be noted that no single analytic method is sufficient to characterize supported NHC compounds; therefore, in practice, a combination of techniques is desirable. Furthermore, those characterization methods mentioned above are not limited to the application described. Other applications of these methods as well as new methods can still be developed. A number of the mentioned examples only provide one approach to prove a certain issue, which is sometimes insufficient and can only be seen as partial evidence. Thus, the use of at least two independent methods to reconcile the findings is recommended.

was used to analyze the diffraction patterns of NPs stabilized by NHCs.310,417 X-ray photoelectron spectroscopy (XPS) is frequently employed to determine the elemental composition as well as the oxidation states of elements on the surface of immobilized NHC compounds. It can thus serve as a diagnostic tool to elucidate the formation of NPs from the immobilized NHC compounds by determination of the electron binding energy of the metals. Glorius et al.42 described the use of XPS analysis to confirm the formation of NHC stabilized Pd(0)-NPs (BE of Pd3d, 335.7 and 340.7 eV) on the surface of the magnetite (Fe3O4) support of compound 596. Li and co-workers136 observed that the oxidation state of the monomeric Au−NHC complex was well-retained in the porous organic polymer supported compounds 462−464 by comparison of the XPS spectra. Signals corresponding to Au 4f7/2 and 4f5/2 binding energies were found at 85.2 and 88.7 eV for the molecular as well as the immobilized complexes, respectively. For the PSsupported NHC compounds synthesized from ligand 195, it was observed that a high NHC loading or more polar precursors lead to an increment of Pd(0)-NPs on the support as revealed by the XPS analysis.200 Thermogravimetric analysis (TGA) is typically applied to evaluate the thermal stability of immobilized NHC compounds and to gain additional physicochemical information, which can be correlated to other analytical methods. For instance, Pleixats and co-workers65 described a significant weight loss during the TGA measurement of supported NHC compounds 498 and 500 between 250 and 500 °C. This observation was ascribed to the decomposition of the organometallic component, and a molar ratio Rh/N of 0.4 for 498 could be calculated from this result, which was close to the expected value of 0.5. Also in TGA experiments Á lvarez et al.28 observed a weight loss attributed to the NHC precursors at 400 °C for the two NHC compounds 264 and 265. Further calculation from these results indicated a nitrogen content of 1.03 mol % for 264 and 1.27 mol % for 265, which was in accordance with the elemental analysis (1.4 mol % for 264 and 2.1 mol % for 265). For the immobilized NHC CO2 adducts prepared from 435− 438, a weight loss of 5% at around 150 °C was detected, which was attributed to the loss of CO2. These results were consistent with the expected composition of the as-prepared NHC CO2 adducts, confirming the quantitative generation from their polyNHC precursors with 1 atm of CO2.59 Powder X-ray diffraction (PXRD) is a rapid analytical technique for the phase identification of crystalline materials and is widely used to determine structural features of immobilized NHC compounds, especially before and after immobilization as well as in the pre- and postcatalytic states. PXRD measurements of immobilized NHC compounds 345 before and after catalytic reactions in comparison to the host material MCM-41 showed no changes, which indicates that the supporting material was quite stable during the reactions, keeping all its primary structural features.124 Likewise, Sumby and co-workers143 compared the MOF-supported NHC compound 530 before and after catalytic reactions (five cycles) by PXRD analysis and observed that the MOF structure of 530 was retained. However, after recycling five times a slightly diminished crystallinity was revealed by broader and less intensive PXRD reflexes. Furthermore, PXRD analysis is employed to evaluate the crystallinity of the supporting materials. Yang and co-workers134 observed three reflexes, which were consistent with a cubic Im3m symmetry, in the

3.3. Characterization Involved in Catalytic Reactions

Apart from the typical analysis of yields (turnovers), substrate scope, and recyclability, a detailed analysis of the catalytic process is also crucial. This provides a more profound understanding of the respective catalyst and, hence, helps with the design of new immobilized catalysts. Basically, four pivotal issues are involved in this evaluation: the analysis of the catalyst before and after catalytic reactions, the determination of the catalytically active species, examination of the extent of catalyst leaching, and a comparison of the immobilized catalyst with its homogeneous analogues. BI


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real, catalytically active species. Indeed, the analysis with an array of experiments is an arduous task in many cases and sometimes it even may not seem worth the effort, especially when working with widely reported catalytic systems such as NHC−Pd and NHC−Ru based catalysts. Nevertheless, a growing tendency of having a detailed analysis of this issue is observed from recent publications; therefore, it is recommended to perform a series of experiments to convincingly study the nature of the catalytically active species in future research. The comparison of the immobilized catalyst with its homogeneous analogues in catalysis is usually conducted to analyze the difference in catalytic performance upon immobilization. In general, a similar or decreased activity is observed for the NHC compounds in heterogeneous form, although the lifetime of the catalyst may be increased. It is noteworthy that some examples report an improved catalytic performance after immobilization due to enhancing effects arising from the supporting material. Examples of such studies are further highlighted in section 4. Concluding, it can be stated that in order to achieve a thorough characterization of supported NHC compounds and complexes certain aspects have to be considered. In order to analyze the NHC moiety on the support, the most important tools are solid state NMR (C2 proton), elemental analysis (NHC loading), and ICP-AES/OES (metal loading). However, many cases allow the application of other analytical techniques. For examining the supporting material, the main experiments comprise solid state NMR (29Si in silica materials), infrared spectroscopy (detecting functional groups), or microscopic techniques such as SEM, which are often combined with EDX spectroscopy. A related technique is XPS, which can also detect surficial elements. Moreover, XRD analysis can reveal the crystallinity of the samples. If catalysis is performed, the abovementioned techniques can often be reapplied in order to verify the stability of the immobilized NHC compound under catalytic conditions.

By characterizing the supported NHC compounds after catalytic reactions with various analytic tools such as TEM, PXRD, XPS, and IR (refer to sections 3.1 and 3.2), the potential chemical and physical changes of the catalyst can be elucidated. Generally, several key objectives such as the retention of primary structural features, the formation of NPs, and the postcatalytic loading of the employed catalyst are addressed. The evaluation of catalyst (or metal) leaching is on the one hand important in order to evaluate the stability of the catalyst, and on the other hand important to identify the catalytically active species. There are two basic approaches to determine the extent of leaching: either by comparison of the metal loading of the catalyst material before and after the catalytic reaction125,258 or by detection of the metal concentration in the reaction filtrate.136,156,188 Of these two, the latter is the more direct and precise way to conduct such a study; thus it is more widely used for the leaching analysis of immobilized NHC compounds. Once leaching of catalytically active metal is determined, the nature of the catalytically active species needs to be determined. Generally, there are three possible catalytic mechanisms that can be in place. First, there are truly heterogeneous systems, where the catalyst is fixed irreversibly to the support and the reaction takes place on its surface. Second, there are so-called “boomerang” systems that release the catalyst into the solution and recapture it once the reaction is completed. This accounts especially for Ru-based metathesis catalysts. Third, there are cases where the catalyst is released into solution but not recaptured, leading to deactivation of the supported catalyst. It is hence a reasonable question to ask what the active catalyst in a reaction is. Is it the immobilized metal complex, a free species that was released from the support, or decomposition products such as metal nanoparticles that were formed in the course of the reaction? With regard to this issue, several review articles have summarized a series of methods that are usually employed to evaluate the heterogeneity (or homogeneity) of the active species in catalysis.424,425 Most commonly applied is the socalled “hot filtration” or split test, where the solid catalyst is removed from the reaction mixture after 30−50% of the total conversion is reached. An increase of the conversion after removal of the solid material indicates dissociation of the catalyst from the surface and thus a homogeneous reaction. It should be noted that a negative leaching result for the reaction filtrate does not necessarily entail the heterogeneity of the catalyst, as the leached catalytic species may redeposit on the support fast enough to be obscured in analysis.426−429 Therefore, other experiments such as poisoning tests may be required to rule out this possibility. Furthermore, catalyst poisons, such as mercury or polymer-based scavengers, which interact and capture metal nanoparticles or other metal species in solution, have been used to address this problem. Davies et al.430 introduced a method which uses an immobilized substrate in a three-phase reaction. Conversion of the second, soluble substrate indicates that the catalytic reaction takes place in solution. With respect to immobilized NHC compounds, it can be noticed that hot filtration and mercury poisoning tests are the most widely used experiments for this purpose. A combination of experiments is recommended to convincingly address this issue, as no single criterion is capable of unambiguously determining the nature of the catalytic species. However, only a few examples reported the use of a combination of metrics to conduct this analysis and many examples were actually without detailed investigation of the

4. CATALYTIC APPLICATIONS OF IMMOBILIZED NHC COMPOUNDS Over the years NHC complexes have proven highly effective in a broad variety of catalytic applications.5,6,10,405,431,432 Among these are prominent examples such as cross-coupling reactions, olefin metathesis, or alkene hydrogenation. By applying immobilization techniques, the unique features of NHC catalysts can be extended by the advantages of heterogeneous catalysis. Particularly the recyclability of a catalyst plays an important role in times of rising scarcity of natural resources and an increasing demand for sustainable chemical processes. In recent years a large number of immobilized NHC complexes have been applied in catalytic reactions. In the following section these will be summarized with regard to the reaction type and the catalytically active metal. 4.1. General Considerations

When catalytic reactions performed by immobilized NHC complexes are evaluated, the typical parameters such as yield, activity, selectivity, and substrate scope are not the only prevalent characteristics. In contrast to homogeneous catalysts there are other factors that can classify a successful immobilized catalyst, for example stability, recyclability, and nature of the catalytic reaction. In general, a big advantage of immobilized catalysts is their easy and at best complete recovery from the BJ


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product solution. For immobilized NHC compounds, catalyst separation can typically be achieved by simple filtration or decantation of the product solution, sedimentation, or centrifugation. If the support is magnetic, e.g. Fe3O4 nanoparticles, the catalyst can also be recovered by magnetic attraction. Identification of the catalytically active species is crucial to provide a more profound understanding of the underlying reaction mechanism aiding rational catalyst design. Four basic aspects should be addressed in the evaluation of a reaction catalyzed by immobilized molecular catalysts: the characterization of the catalyst before and after the catalytic reaction, the identification of the catalytically active species, the catalyst leaching behavior, and the catalytic performance of the immobilized catalyst in comparison to its homogeneous analogues. A summary of the methods used to achieve this is given in section 3. As the leaching characteristics of the catalysts can be determined by two different approaches, percentage amounts in the tables refer to the loss of catalytically active metal during the catalysis and concentrations (usually given in parts per million or parts per billion) refer to metal contamination of the reaction solution or the products, respectively. In the following subsections examples of the respective reactions catalyzed by immobilized NHC compounds will be summarized in tabular form.

Scheme 159. General Reaction Scheme of the Suzuki− Miyaura Reaction and Commonly Employed Substrates

However, also self-supported catalysts have been used successfully, exhibiting remarkably low leaching tendencies.163−165,168 Furthermore, it can be seen in Table 8 that in most Suzuki−Miyaura reactions polar solvents such as DMF and H2O are employed. Apart from the solvent, there are high discrepancies in terms of reaction conditions, which does not allow a comprehensive comparison of catalytic performance. Reaction times range from 5 min up to 24 h, temperatures between room temperature and 160 °C have been applied, and the catalyst amount varies strongly. To evaluate the performance of a catalytic system, the substrate range is one of the most significant indicators. As indicated above, aryl iodides react more readily in the initial oxidative addition step than bromides and chlorides. Thus, the latter can be considered the more challenging substrates, yet they have been used in Suzuki−Miyaura cross-coupling reactions catalyzed by immobilized Pd−NHC catalysts in several cases (refs 50, 68, 86, 89, 100, 103, 108, 111, 114, 117, 133, 135, 151, 163−165, 177, 193, 201, 219, 220, 240, 291, 293, 296, 415). Silica supported Pd−NHC compounds even allowed coupling reactions of donor-substituted and sterically hindered aryl chlorides in good yields.134,135 A variety of different aryl chlorides bearing electron-donating substituents have also been tested in coupling reactions with phenylboronic acid using norbornene based catalysts.50 In all reactions high yields were reached. In recycling experiments, however, yields declined drastically after only two runs due to decreasing solubility of the catalyst. Instead of aryl halides, arylsulfonyl chlorides and 1aryltriazenes can also be used as substrates for cross-coupling reactions with boronic acids. Luo et al.435 reported a polystyrene supported Pd−NHC complex, which catalyzes the coupling of phenylboronic acid to various substituted phenylsulfonyl chlorides in high yields. The same catalyst was later used to promote the coupling of 1-aryltriazenes and arylboronic acids.358 An immobilized Pd−NHC catalyst for carbonylative Suzuki−Miyaura cross-coupling reactions was reported by Bhanage et al.205 In the presence of gaseous CO, aryl iodides and phenylboronic acids reacted to benzophenones in excellent yields. Recycling of the immobilized catalyst is a very important aspect of heterogeneous catalytic reactions. Usually the catalyst is filtered off or separated by centrifugation after the reaction is finished. In some cases iron containing nanoparticles were used as supporting material, allowing the separation by application of an external magnetic field.82,114,201,297,434 Thus, the loss of catalyst material during recovery was significantly reduced. Recycling tests usually comprise up to 10 reaction cycles, and in many cases a loss of performance becomes visible within these first runs. More extensive recycling tests have only been

4.2. Cross-Coupling Reactions

Cross-coupling reactions have received great interest since the late 20th century and comprise the formation of a C−C bond between two hydrocarbon fragments by a metal catalyst.433 The general reaction mechanism consists of three basic consecutive steps: oxidative addition, transmetalation, and reductive elimination. The immobilization of palladium complexes, which serve as precatalysts for cross-coupling reactions, has become an important research area in the past years in both academia and industry. It significantly facilitates the separation of the catalyst from the product, and thus rising palladium prices and product purity requirements for pharmaceutical applications are met.53 In addition to Pd−NHC complexes there are only a few examples of immobilized metal−NHC complexes that have been used for cross-coupling catalysis. Among these are gold, copper, and nickel compounds. In comparison to other ligands, such as phosphines, NHCs provide a high electron density at the central metal atom as they are strong σ-donors and allow only a low degree of π-backbonding. This facilitates the initial oxidative addition step. 4.2.1. Suzuki−Miyaura Reaction. The Suzuki−Miyaura cross-coupling of aromatic boronic acids and halogens is one of the most thoroughly examined reactions with regard to immobilized NHC catalysts. The most commonly used substrates are depicted in Scheme 159. Due to the comparatively low bond energy of aryl iodides, they readily undergo oxidative addition to the Pd catalyst; bromides and chlorides on the other hand are less reactive. Furthermore, substitution of the aryl moiety by electron-withdrawing substituents enhances the substrate reactivity. Table 8 provides an overview of Suzuki−Miyaura cross-coupling reactions catalyzed by immobilized NHC transition metal complexes, including the respective reaction conditions and experimental yields. Most of the catalysts in Table 8 exhibit the same fundamental structure, where the NHC ligand is bound covalently to the support and thus links the supporting material to the metal. BK


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Table 8. Suzuki−Miyaura Cross-Coupling Reactions Catalyzed by Immobilized NHC Compoundsa substrate I C6H5I p-Me-C6H4Cl C6H5I C6H5Br p-MeO-C6H4Br C6H5I p-CHO-C6H4Br C6H5I p-Me-C6H4Cl m-NO2-C6H4-SO2Cl C6H5Br p-CHO-C6H4Br p-Me-C6H4I p-Me-C6H4Cl p-MeO-C6H4Br p-MeCO-C6H4Br p-MeCO-C6H4Br p-MeO-C6H4Cl p-NO2-C6H4Br p-MeO-C6H4Br C6H5I C6H5Br p-MeO-C6H4Br p-CHO-C6H4Cl C6H5Br p-MeO-C6H4Cl p-CN-C6H4Cl C6H5Cl C6H5Br 1-(3-nitrophenyl)-2-(pyrrolidin-1-yl) diazene p-CHO-C6H4Cl C6H5Cl C6H5I C6H5I p-Me-C6H4Cl p-Me-C6H4Cl C6H5Br p-MeOC-C6H4Cl p-MeOC-C6H4Br p-MeOC-C6H4Cl p-MeOC-C6H4Br C6H5Br p-MeO-C6H4Br p-Me-C6H4Br p-MeO-C6H4Br p-MeO-C6H4Br naphthyl triflate C6H5I C6H5Br C6H5Br C6H5I p-MeO-C6H4Br p-MeO-C6H4Br p-MeOC-C6H4Br C6H5I p-Me-C6H4Br C6H5Br p-MeO-C6H4Br p-Me-C6H4Br

substrate II

solvent

C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 p-MeO-C6H4B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 o-Me-C6H4B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 p-Me-C6H4B(OH)2 p-Me-C6H4B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2

H2O/DMF dioxane H2O/DMF DMA H2O/DMF H2O/DMF H2O H2O dioxane THF H2O/DMF H2O H2O/iPrOH dioxane H2O/EtOH H2O/DMF H2O i PrOH H2O/DMF H2O/DMF H2O H2O/DMF H2O H2O H2O/EtOH i PrOH H2O/DMF H2O/DMF H2O/DMF dioxane

C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 indole boronic acid C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2 C6H5B(OH)2

i

PrOH PrOH H2O/DMF H2O H2O H2O C6H5Me i PrOH H2O/DMF i PrOH H2O/DMF toluene H2O H2O toluene H2O/DMF THF EtOH H2O/EtOH H2O H2O/DMF H2O H2O/MeOH H2O H2O/EtOH H2O/DMF H2O/PEG-400 H2O/DMF H2O i

BL

[cat.] (mol %)

yield (%)

leaching

recycling (no. runs)

1.2 1.5 1 1 0.4 1 0.1 2 1 0.625 0.5 0.1 2 0.5 0.1 1 1 0.1 0.1 0.2 2.5 0.75 0.5 0.05 0.01 3 2 1 0.2 2

93 85 96 57 99 95 98 91 99 87 99 90 90 99 96 94 98b >99 100 100 96 52 98 92 99 93 100 57 33 92

ref

− − − 3 ppb − n.o. − n.q. n.q. 0.21% n.o. − − − 0.5% 1−3% − 7% n.o. 22.9 ppm n.o. 4% 8.8% − − 0.13% n.o. − n.o. 0.4

3 4 3 4 5 10 − 5 3 5 4 − 5 − 6 5 4 − 6 3 8 − 5 6 10 5 6 − − 8

203 117 46 278 256 47 183 31 50 359 80 184 102 151 81 219 150 415 89 107 139 202 82 163 83 220 291 100 34 358

0.5 0.5 0.5 0.75 0.05 0.05 10 0.5 0.2 0.32 0.2 0.5 0.25 0.5 3 0.1 2 0.05 0.25 0.5 0.002 0.025 0.2 0.01 0.1 1 0.1 0.75 0.05

99 78 100b 100 91 78 98 92 >99b 87 100b >99 71 75 43b 99 98 80 93 97 91 100 96 100 98 89b 92 97 95

99 95 95 87 95 >93 95 >93 95 100 100 95 95 99 95b >93 94 86 64 97 45b >97b 98b >99 80 100 100b 90 96 85 RT

38 ppm 0.3% n.q.

Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic

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