Synthesis and structural characterization of 20-membered macrocyclic rings bearing trans-chelating bis(N-heterocyclic carbene) ligands and the catalytic activity of their palladium(II) complexes

Abstract

Macrocycles consisting of a 20-membered ring containing two imidazolium salt functionalities and of the formula [PhCH₂N(CH₂CH₂CH₂)Im(CH₂CH₂CH₂)₂][Br]₂ (Im = imidazole = 3a, benzimidazole = 3b) were synthesized in 70–75% yields. These salts serve as precursors to macrocycles containing two N-heterocyclic carbene (NHC) moieties. Reaction of the macrocyclic salts 3a and 3b with silver oxide afforded macrocyclic-bis(NHC)silver(I) complexes 4a and 4b. Single-crystal X-ray diffraction studies of macrocyclic-bis(NHC)silver(I) complex 4a revealed a tetranuclear silver core with a short Ag-Ag distance (2.9328 Å). Complexes 4a and 4b serve as carbene transfer reagents to Pd. The treatment of macrocyclic-bis(NHC)silver(I) complexes 4a and 4b with one equivalent of PdCl₂(MeCN)₂ in methylene chloride afforded square-planar trans-macrocyclic-bis(NHC)Pd(II)X₂ complexes 5a and 5b. Preliminary screening of these palladium complexes showed they are competent precatalysts for Heck and Suzuki coupling reactions.

Graphical Abstract

20‐membered macrocyclic rings containing NHCs and amines were synthesized, and their late metal coordination chemistry explored.

Introduction

After the isolation of the first stable, free N-heterocyclic carbenes (NHCs) by Arduengo,¹ NHCs have been used widely in homogenous catalysis and coordination chemistry. Due to their strong σ-donating properties, NHC ligands bind strongly to a variety of metals and stabilize a wide range of metal oxidation states.^2,3,4 NHC complexes owe their high thermal stabilities to their strong metal-carbon bonds, and NHC ligands are unique due to their lack of π-accepting properties.^5,6 For these reasons, NHCs have found a wide range of applications where phosphine ligands are not desirable.^7–,8,9,10 The NHC moiety has been shown to coordinate to most transition metals and has been used as a supporting ligand for a wide variety of catalysts with excellent performance in many important reactions.^6,11–12,13 NHCs have been shown to coordinate with Pd, generating competent precatalysts for C-C bond-forming reactions.^{14–,15,16,17,18,19,20,21,22}

Although there has been an abundance of work on the synthesis and reactivity of NHC-metal complexes, there is still significant interest in the development of new macrocyclic NHC ligands.^{2,3,5,12,14,20,23,24} There is an abundance of research on cis-bidentate-chelating NHC ligands with Pd; fewer ligands have been reported that coordinate in a trans fashion, and still fewer within a closed (macrocyclic) scaffold.^{18,25–,26,27,28,29} The first trans-chelated bis(NHC) complexes of Pd and Ni possessing binaphthyl backbones were reported by RajanBabu.³⁰ This ligand formed a mixture of cis- and trans-chelated Pd NHC complexes. The cis/trans mixture is common and cannot be separated in most cases.^27,31 Pd complexes with bidentate trans-chelating NHCs have been shown to be active catalysts for C-C coupling reactions.^32,18

Douthwaite et al. discovered flexible tridentate bis-NHC amino ligands where the NHC moieties are connected by a flexible five-atom linker consisting of four methylene groups and an amino functionality (CH₂CH₂NRCH₂CH₂). They showed that these ligands bind to the Pd center as a tridentate pincer with coordination of the central amine.^32,33 Hazari et al. reported a family of bidentate trans-chelating NHC ligands with flexible propyl linkers incorporating a tertiary amine. They have shown that these ligands easily bind to Pd in a bidentate trans-spanning fashion with no coordination to the central amine, forming a 12-membered palladacycle (Chart 1, i).¹⁸ These Pd complexes are active towards Heck and Suzuki reactions.^18,32,33

Chart 1.

Previously reported polydentate and macrocyclic (NHC)Pd(II) complexes

A macrocyclic complex with a 15-membered ring and a bidentate cyclophane geometry containing a butane linker was reported (Chart 1, ii) by Hahn.³⁴ A plethora of small 15-membered macrocyclic complexes^31,34,35 or larger 28–38 membered macrocyclic ligands^36,37 with tridentate coordination systems have been reported, but only a handful of “intermediate” sized macrocyclic ligands are in the literature. Chaplin and co-workers have synthesized a series of 19–23-membered CNC macrocyclic pincer ligands consisting of bis(imidazolium)-lutidine salts with octa-, deca- and dodecane spacers (Chart 1, iii). These CNC macrocyclic pincer ligands are converted to Ag carbene complexes that serve as transmetalating agents to produce cationic Pd(II) chloride complexes.³⁸ Pd complexes comprised of 16-membered macrocycles containing two or more NHC’s have been synthesized by Pöthig and Kühn (Chart 1, iv)³⁹ in addition to macrocycles containing other transition metals.⁴⁰ These macrocyclic systems differ from the others discussed here because they are rigid and do not contain any available coordination sites at the metal. Other groups have synthesized macrocycles containing two or more NHC moieties of similar size.⁴¹ Additionally, Kühn and co-workers have synthesized larger more flexible systems that are analogous to their macrocyclic systems but do not consist of a closed macrocycle.⁴² These flexible ligand systems can coordinate a variety of metals and some can coordinate several metal centers.⁴³

As mentioned above, some of these polydentate ligands have been observed to adopt a variety of coordination modes by displacement of inner sphere halides.^38,32,33 The ligands in this study were chosen to have a larger ring structure than those of Hahn and co-workers. These larger ring structures are expectedly fluxional. Additionally, the larger ring structures used in this study differ from Chaplin and Hahn’s previous work because these macrocycles contain four possible coordination sites, enabling these macrocycles to adopt a number of coordination modes and stereochemistries.

In this study, we examined the coordination chemistry and reactivity of intermediate-sized 20-membered macrocyclic rings containing two tertiary amines and two NHC moieties derived from imidazole and benzimidazole. We synthesized and characterized the silver(I) complexes of these macrocyclic ligands for use as carbene transfer / transmetalating agents. We surveyed the coordination chemistry of these ligands with Pd as a first step toward understanding whether these intermediate-sized rings would adopt a mixture of stereoisomers (cis / trans NHCs) or form mixtures of coordination modes to the metal (κ², κ³ etc.). In particular, the displacement of inner-sphere halides to form cationic metal species is of interest for Pd and other transition metals. This work lays the foundation for studies of the coordination chemistry of these intermediate-sized macrocycles with a broad array of metals. We found that these macrocycles adopt trans-NHC configurations when coordinated to Pd. The flexible trans amino ligands connected to the NHCs by propyl chains were not found to displace inner sphere halides of the Pd complexes in the solid state. We have characterized these Pd complexes and screened them for activity as precatalysts for Suzuki-Miyauri and Heck cross-coupling reactions.

Results and Discussion

Scheme 1 summarizes the synthesis of the bis-imidazole amine and bis-benzimidazole amine compounds (2a-2b) that comprise half of the target 20-membered macrocycles as well as macrocycles 3a and 3b. Bis(ester) (A) was synthesized from commercially available benzylamine and ethyl acrylate utilizing a Michael addition.⁴⁴ Reduction of A with LiAlH₄ produced bis(alcohol) (B),¹⁸ which was converted into the bis-bromide starting material (1) by refluxing with concentrated HBr for 24 hours.⁴⁵ N-Benzylbis(3-bromopropyl)-imidazole (2a) and N-benzylbis(3-bromopropyl)benz-imidazole (2b) were obtained by the reaction of N-benzylbis(3-bromopropyl)amine 1, sodium hydride and imidazole or benzimidazole, respectively, in THF (Scheme 1). Both compounds 2a and 2b are colorless viscous liquids.

Scheme 1.

Synthesis of macrocyclic ligand 3a and 3b

The cyclization reaction between 1 and N-benzylbis(3-bromopropyl)-imidazole 2a or N-benzylbis(3-bromopropyl)benzimidazole 2b yields the corresponding cyclophane-like 20-membered macrocyclic bisimidazolium bromide salts 3a and 3b (Scheme 1). The cyclization reactions were performed at low concentrations (~100 mM) to prevent possible oligomerization side reactions.¹⁸

Proligand 3a is a hygroscopic white solid, which is soluble in polar solvents such as dichloromethane, acetonitrile, and THF and insoluble in nonpolar solvents such as toluene, hexanes, and petroleum ether. Unlike 3a, the proligand 3b is stable in air and is soluble in chloroform, but is insoluble in methylene chloride, acetonitrile, and dimethyl sulfoxide. The overall yield of 3a-3b is 50 to 60%.

A crystal suitable for X-ray crystallography of 3a was obtained by slow diffusion of chloroform into a solution of 3a in dichloromethane (Figure 1). The X-ray structure confirms macrocycle formation. ¹H NMR spectroscopy of 3a in CD₂Cl₂ shows three resonances at δ 4.05 (triplet), δ 2.49 (triplet) and δ 1.97 (quintet) ppm. These resonances correspond to the three methylene groups of the four propyl chains (NCH₂CH₂CH₂N) present in the macrocyclic proligand 3a Similarly, three resonances were observed for the methylene protons of the propyl chains of 3b in CDCl₃ at δ 4.64 (triplet), δ 2.83 (triplet) and δ 2.65 (quintet) ppm. These data show that the solution conformations of 3a and 3b are either highly fluxional or are consistent with the symmetric structures observed in the solid state.

Figure 1.

Thermal ellipsoid plot of the diimidazolium salt, C₃₂H₄₄ Br₂N₆∙2(CHCl₃), 3a (50% ellipsoids). Hydrogen atoms, bromide anions and solvent molecules have been omitted for clarity. The two sides of the macrocycle were found to be equivalent by symmetry.

The ¹H NMR resonances of the imidazolium 2-position protons (NCHN) for 3a and 3b appear as singlets at δ 10.77 ppm and δ 11.33 ppm, respectively. ¹³C NMR shows the C-H resonances of the imidazolium 2-position at δ 139 ppm (3a in CD₂Cl₂) and δ 144 ppm (3b in CDCl₃). These chemical shifts are consistent with similar systems in the literature.⁴⁶

Attempts to deprotonate proligand 3a to form a macrocyclic bis-NHC compound were not successful on large scales. An NMR tube reaction between proligand 3a and excess sodium hydride in DMSO-d₆ showed the formation of free bis-NHC 3c in situ under nitrogen atmosphere at room temperature. The in situ generation of the free bis-NHC 3c was confirmed by a characteristic downfield ¹³C NMR peak at δ 208 ppm corresponding to a free carbene. Additionally, the ¹H NMR signal for the imidazolium 2-position previously observed at δ 9.19 ppm is no longer present, implying formation of the free carbene 3c. The free bis-NHC ¹³C NMR carbene chemical shift observed is comparable to the isolable NHC (δ 211.43 ppm in C₆D₆) reported by Arduego et al.¹ and other NHCs.⁴⁶

Attempts to isolate the free carbene furnished an intractable viscous dark red oil consistent with the literature.³² This oil can be generated through deprotonation of the imidazolium salt 3a using bases such as t-BuOK and/or NaH. However, subsequent work-up results in decomposition and the formation of multiple products. As reported previously,¹² this product mixture was likely formed by deprotonation of the benzylic positions of the macrocycle and deprotonation of the methylene groups adjacent to the imidazole rings.

Direct reaction of free carbenes generated in situ by treatment of a mixture of imidazolium salt and strong base with PdCl₂(MeCN)₂ has been shown to yield metalated product.⁴⁷ Direct reaction of in situ generated 3c with PdCl₂(MeCN)₂ yielded a mixture of products. Several bases were screened for direct deprotonatation and metalation of the ligand including n-BuLi, NaH, t-BuOK. All these reactions yielded a mixture of products. Reaction of 3b with t-BuOK in THF with PdCl₂(MeCN)₂ also yields a complex product mixture. Additionally, direct metalation of 3a and 3b with PdCl₂(MeCN)₂ did not occur after refluxing 16 hours in methylene chloride.

Ag complexes

Several groups have used transmetalation from Ag complexes as a strategy to efficiently synthesize other metal NHC complexes.^{38,48–49,50,51,52,53,54,55,56,57} Bis(NHC)silver(I)bromide complexes 4a and 4b were prepared as ligand transfer agents (Schemes 2 and 3) by the reaction of imidazolium salts 3a and 3b with excess silver oxide in methylene chloride. Upon deprotonation of 3a and 3b, the target 20-membered macrocyclic bis-NHC-bis-amino ligands are formed and coordinate to Ag(I).

Scheme 2.

Synthesis of bis(NHC)Ag(I)bromide complexes 4a

Scheme 3.

Synthesis of bis(NHC)Ag(I)bromide complexes 4a and 4b

Analytically pure, light-sensitive Ag complexes 4a and 4b were obtained in high yield as white crystalline solids. After the reaction of silver oxide with solutions of 3a and 3b for 24 hours, the imidazolium 2-position ¹H NMR resonances were no longer present. Additionally, the characteristic ¹³C NMR signals of the C-H 2-position of imidazolium compounds 3a and 3b were shifted downfield from 139 and 144 ppm to 180 and 181 ppm for the Ag complexes 4a and 4b, respectively. This downfield shift is characteristic of Ag-NHC complexes.^18,46

The ¹H NMR spectra of 4a and 4b show four methylene resonances consistent with a benzylic methylene group and three methylene resonances from the propyl chains of the macrocycle. These data show that both sides of the macrocycle and all four propyl chain linkers are equivalent, implying that the Ag carbene macrocycle is fluxional in solution. The absence of Ag-¹³C coupling also suggests that 4a and 4b linkers are fluxional and that the Ag-carbene bond is labile on the NMR timescale.^57,58,59,60

Ag-NHC complexes have been shown to exhibit a variety of binding modes in the solid state.^18,25,61 In order to determine the nucleariety of the complexes, the structures were investigated by single-crystal X-ray diffraction analysis.

A colorless crystal suitable for X-ray crystallography of 4a was obtained by slow diffusion of chloroform into a saturated dichloromethane solution of 4a. As shown in Figure 2, 4a exists as a dimer consisting of two crystallographically equivalent macrocyclic ligands, each chelating a single silver atom through the NHC moieties of the macrocycle. These Ag-macrocycle complexes are bridged by a dianionic core which consists of a [Ag₂Br₄]^2- unit. This bridging [Ag₂Br₄]^2- unit is well known in the literature.^{18,25,50,59,61,62–,63,64} The C(4)-Ag(1)-C(13) angle (NHC-Ag NHC angle) was found to be 163.4°, showing the coordinated Ag atom protruding from the center of the macrocycle. Notably, the distance between the chelated Ag atoms within the macrocycles and the Ag atoms of the [Ag₂Br₄]^2- core is only is 2.9328(18) Å, which is shorter than bond lengths reported for similar Ag complexes and is indicative of Ag-Ag bonding.^18,25,58 This short Ag(1)-Ag(2) bond distance may explain the acute angle observed for (C(4)-Ag(1)-C(13), as if the bonding to the Ag₂Br₄^2- core is pulling the chelated Ag away from the center of the macrocycle.

Figure 2.

Thermal ellipsoid plot of silver complex 4a with thermal ellipsoids at 50% probability. Hydrogen atoms have been removed for clarity. Selected bond distances (Å) and bond angles (°): Ag(1)-Ag(2) = 2.9327(18), Ag(2)-Br(1) = 2.6802(19), Ag(2)-Br(2) = 2.5370(19); C(4) -Ag(1)-Ag(2) = 123.0(3), Br(2)-Ag(2)-Br(1) = 126.42(6), Br(2)-Ag(2)-Ag(1) = 91.60(5)

A crystal suitable for single-crystal X-ray diffraction of 4b was obtained by slow evaporation of a saturated dichloromethane solution of macrocyclic-bis(NHC)silver(I) bromide 4b. In the solid state structure of 4b (Figure 3), two structurally equivalent cationic macrocyclic-bis(NHC)silver(I) complexes are linked through an anionic AgBr₂⁻ core. A second AgBr₂⁻ unit is found in the unit cell; however, no close contacts are observed to the second anion. The AgBr₂⁻ unit linking the two macrocyclic Ag complexes appears to be perfectly linear. The Br(1)-Ag(1)-Ag(2) angle of 97.94° shows that the bridging Ag(1) atom possess a slightly distorted square planar geometry. Unlike 4a, the Ag(1)-Ag(2) bond distance of 3.004(3) Å is consistent with literature reports of Ag-Ag bond distances in similar compounds.⁶¹ Additionally, the C(14)-Ag(2)-C(1) angle was found to be 170.30°, which is larger than the analogous angle in 4a. This AgBr₂⁻ anionic core bridging between Ag-NHC complexes is commonly seen as part of larger coordination-polymer crystal systems in the literature.⁶¹ However, it does not appear to be as common for dimeric structures.⁶⁵

Figure 3.

Thermal ellipsoid plot of silver complex 4b with thermal ellipsoids at 50% probability. Hydrogen atoms, AgBr₂⁻, and solvent molecules have been removed for clarity. Selected bond distances (Å) and bond angles (°): Ag(1)-Br(1) = 2.450(4), Ag(1)-Ag(2) = 3.005(3); Ag(2’)-Ag(1)-Ag(2) = 180.0, Br(1)-Ag(1)-Ag(2’) = 97.73(8), Br(1’)-Ag(1)-Br(1) = 180.00(6).

Palladium complexes

Metal acetates have been used to synthesize NHC complexes without isolation of the free carbene. Hermann et al. reported the first structurally characterized trans-bis(NHC)Pd(II)Cl₂ complex that was prepared by direct deprotonation of imidazolium salts with palladium acetate^66,34,64 In our hands, the direct deprotonation of imidazolium salts 3a and 3b with palladium(II) acetate and platinum(II) acetylacetonate at high temperature leads to inseparable mixtures of products.

Pd complexes 5a and 5b were prepared by the reaction of bis(NHC)silver(I) bromide complexes 4a and 4b with PdCl₂(MeCN)₂ (Scheme 4). After 20 hours at 60 °C, the reaction forms silver bromide as a pale yellow precipitate. Bis(NHC)Pd(II)Cl₂ complexes 5a and 5b were obtained as white solids after removal of silver bromide by filtration and evaporation of solvent (Scheme 4).

Scheme 4.

Synthesis of bis(NHC)Pd(II)Cl₂ complexes 5a and 5b

A crystal of 5a suitable for X-ray crystallography was obtained by slow diffusion of pentane into a saturated dichloromethane solution of the Pd compound. The X-ray structure (Figure 4) confirms that the NHC moieties of the macrocycle coordinate in a trans fashion. 5a was found to possess a C₂-symmetric structure. Additionally, no coordination is observed from the pendant amines in the macrocycle to the Pd center. The [C(1)-Pd-C(1’)] angle was found to be 180.00°, and the Pd center has a nearly ideal square-planar geometry, in contrast to Hazari’s similar complexes.¹⁸ Additionally, the observed bite angle of the ligand is larger than that of many Pd complexes with trans-spanning phosphine ligands.⁶⁷ The two pendant amine groups within the macrocycle are positioned directly above and below the Pd-NHC coordination plane, as if approaching the Pd along the idealized z-axis of the square-planar complex. The amine N-Pd distance was found to be 3.746(2) Å.

Figure 4.

Thermal ellipsoid plot of 5a with thermal ellipsoids at 50% probability. Hydrogen atoms have been removed for clarity. Selected bond distances (Å) and bond angles (°): Pd(1)-Cl(1)= 2.3387(9), Pd(1)-C(1) = 2.031(3), C(1)-N(1) = 1.352(4); Cl(1)-Pd(1)-Cl(1’) = 180.00(2), C(1)-Pd(1)-Cl(1) = 90.05(9), C(1)-Pd(1)-C(1’) = 180.0

X-ray diffraction of 5b (Figure 5) shows a trans configuration for the NHC moieties of the macrocyclic ligand with no coordination of the pendant amines to Pd. Additionally, X-ray diffraction shows that 5b exists as a mixed halide species with a stoichiometry of C₄₀H₄₆N₆PdCl_1.57Br_0.43. ¹H NMR spectra of typical preparations of 5b show only one set of peaks for 5b. HR-FT-ICR-MS shows the monochloride mono cation [C₄₀H₄₆ClN₆Pd]⁺): m/z 751.2508 (calcd) and 751.2528 (found). Mixtures of halomers have been previously observed as a result of various synthetic methods to generate late metal carbene species including transmetalation from silver salts.⁶⁸

Figure 5.

Thermal ellipsoid plot of carbene complex 5b with thermal ellipsoids at 50% probability. Hydrogen atoms, a disordered phenyl group and a partially occupied Br have been omitted for clarity. Selected bond distances (Å) and bond angles (°): Pd-Cl(1)= 2.241(16), Pd-C(1) = 2.027(12), C(1)-N(1) = 1.343(15); Cl(1)-Pd(1)-Cl(1’) = 180.0, C(1)-Pd(1)-Cl(1) = 89.3(6).

The structure of 5b is comparable to the solid-state structure of 5a (Figure 4). Both structures show nearly ideal square-planar coordination of Pd. The stereochemistry of the Pd center is likely related to the ring size of the macrocycle, specifically, the number of methylene linkers in the chains between the two NHC moieties. The cis isomer appears to be favored in shorter linkers.^18,64 A minimum of six methylenes as linker is suggested to favor trans coordination by DFT studies,¹⁸ consistent with our observations.

The macrocyclic ligands in 5a and 5b appear to completely envelop the Pd center. The torsion angles between the square planes of the Pd(II) center and the planes of the NHC rings are 115.5° and 108.9°, respectively. Effectively, the Pd-Cl bonds protrude from the plane of the macrocyclic structure surrounding the Pd center. The distances between the Pd and amine N atoms in 5a and 5b are 3.746 Å and 3.825 Å, which are well beyond the sum of the van der Waals radii of Pd and N (3,18 Å).^73,69 It is reasonable to assume that these large distances allow ample space for reactions to occur at Pd (vide infra).

Pd-catalyzed coupling reactions

The Suzuki reaction, the coupling of an aryl halide with phenylboronic acid, is one of the most widely known cross-coupling reactions.⁷⁰ The macrocyclic-trans-bis(NHC)PdCl₂ complexes 5a and 5b were screened for activity as precatalysts for Suzuki and Heck cross-coupling reactions. The reaction conditions for the Suzuki and Heck reactions are described in the experimental procedures and were modified from the literature.^18,71 The products were detected by gas chromatography-mass spectroscopy (GC/MS) and the percentage yield was calculated by comparing the proton resonance of the product with the known proton resonance of an internal standard (1,3,5-trimethoxybenzene).

The Suzuki coupling of aryl halides with phenylboronic acid (Scheme 5) was performed using 1 mol % of the Pd precatalyst (Table 1).

Scheme 5.

Suzuki coupling reaction between aryl halides and phenylboronic acid

Table 1.

Suzuki coupling of aryl halides with phenylboronic acid using (5a-5b)

Entry	Substrate	Time (h)	Cat.	Yield (%)a
1.	4-bromonitrobenzene	3	5a	>99
2.	4-bromonitrobenzene	3	5b	>99
3.	bromobenzene	3	5a	61
4.	bromobenzene	3	5b	50
5.	bromobenzene	6	5a	96
6.	4-iodoanisole	16	5a	96
7.	4-iodoanisole	10	5b	>99
8.	4-bromotoluene	3	5a	97
9.	4-bromotoluene	3	5b	70
10.	4-chlorotoluene	24	5a	37
11.	4-chlorotoluene	24	5b	9
12.	4-chloroacetophenone	8	5a	52
13.	4-chloroacetophenone	8	5b	>99
14.	4-chloroacetophenone	17	5a	70
15.	4-bromoacetophenone	3	5a	>99
16.	4-bromoacetophenone	3	5b	>99
17.	4-bromotoluene	7	5a	64b
18.	4-bromonitrobenzene	7	5b	9b
19.	4-bromonitrobenzene	7	5a	4b
20.	4-bromonitrobenzene	24	none	0

^aThe average of two runs determined by ¹H NMR using an internal standard. No increase in yield was observed if the reaction time was increased. Conditions: 1 mol % of precatalyst, Cs₂CO₃ (0.90 mmol), substrate (0.20 mmol), phenylboronic acid (0.45 mmol) and 1,4-dioxane (1.5 mL) at 100 °C under N₂. ^bPrecatalyst loading: 0.1 mol %.

^bPrecatalyst loading: 0.1 mol %.

The bidentate macrocyclic-trans-bis(NHC)PdCl₂ complexes 5a and 5b were demonstrated to be competent precatalysts for Suzuki cross-coupling reactions. Various aryl halides, including aryl chlorides, bromides and iodides, were coupled with phenyl boronic acid in moderate to excellent yields (Table 1).

Precatalysts 5a and 5b both facilitate coupling of the less reactive unactivated aryl chlorides with phenylboronic acid (Table 1, Entries 10, 11) in low to moderate yields. Activated aryl-chlorides show moderate to excellent yields (Table 1, Entries 12–14). In these data, 5a and 5b exhibit higher activity than similar reported non-macrocyclic catalysts.¹⁸ Due to the apparently quantitative coupling of aryl bromides using precatalyst 5a and 5b, the couplings of 4-bromonitrobenzene and 4-bromotoluene with phenylboronic acid were selected for further investigations at lower precatalyst loads (0.1 mol %). At 0.1 mol % precatalyst loading, 4-bromotoluene was found to afford appreciable yield (Table 1, Entry 17) but 4-bromonitrobenzene gave poor yield (Table 1, Entries 18–19).

Next, the macrocyclic-trans-bis(NHC)PdCl₂ complexes were screened as precatalysts for the Heck coupling reaction (Scheme 6). Initially, 4-iodoacetophenone was combined with n-butyl acrylate in the presence of 0.1 to 0.02 mol % of precatalysts 5a and 5b.

Scheme 6.

Heck coupling reaction between aryl halides and n-butyl acrylate

Our data shows that 5b generates a more active catalyst than 5a, showing 10–16% higher yields for the Heck coupling reaction (Table 2). A possible explanation for this observation could be the absence of vinylic imidazole protons on the benzimidazole heterocycle. Imidazole C-H protons have been postulated to be acidic enough to react with bases during catalysis and serve as an additional route to catalyst decomposition.⁷²

Table 2.

Heck reaction between n-butyl acrylate and 4-iodoacetophenone

Entry	Cat. (mol%)	time (h)	Yield (%)a	TOFb
1.	5a (0.1)	1	50	510
2.	5a (0.1)	1.5	60	400
3.	5a (0.1)	4	70	670
4.	5a (0.02)	1	38	2037
5.	5b (0.1)	1	66	660
6.	5b (0.1)	1.5	85	567
7.	5b (0.1)	4	82	1025
8.	5b (0.02)	1	46	2378

^aYield determined by ¹H NMR using an internal standard; only the trans isomer was observed.

^bTurnover frequency (TOF) = (mol of product)/((mol of Pd) h). Conditions: All reactions used 4-iodoacetophenone (0.2 mmol), Na₂CO₃ (0.24 mmol), tetra-n-butylammonium bromide (0.02 mmol), n-butyl acrylate (0.4 mmol, 2 equivalents), dimethyl-acetamide (1.5 mL), 140 °C.

Table 3 summarizes a survey of substrates for the coupling of aryl halides with n-butyl acrylate in the presence of precatalyst 5b (Scheme 6). Various aryl iodides and aryl bromides can be coupled with n-butyl acrylate efficiently using 5b; however, in contrast to the Suzuki coupling reaction, aryl chlorides show low reactivity.

Table 3.

Heck coupling of aryl halides with n-butyl acrylate using 5b

Entry	substrate	mol%	time (h)	Yield (%)a
1.	4-bromonitrobenzene	0.1	4	>99
2.	4-bromoacetophenone	0.1	1	51
3.	4-bromoacetophenone	0.02	1	32
4.	4-bromotoluene	0.1	7	47
5.	bromobenzene	0.1	8	42
6.	4-iodoanisole	0.1	1	50
7.	4-chlorotoluene	0.1	16	0
8.	4-chlomoacetophenone	0.1	16	4
9.	4-bromonitrobenzene	none	24	0

^aYield determined by ¹H NMR using an internal standard. Only the trans isomers were observed. Conditions: All reactions used 0.1 mol % of precatalyst 5a and 5b, aryl halide (0.2 mmol), Na₂CO₃ (0.24 mmol), tetra-n-butylammonium bromide (0.02 mmol), n-butyl acrylate (0.4 mmol, 2 equivalents), dimethylacetamide (1.5 mL), 140 °C.

The Heck coupling reaction using 0.1 mol % of precatalyst 5b shows high yield with trans selectivity for 4-bromonitrobenzene (Table 3, Entry 1). 4-Bromobenzene appears sluggish compared to 4-bromoacetophenone, but still gives moderate yield at longer reaction times using 0.1 mol % precatalyst (Table 3, Entries 2–5). 4-Bromoacetophenone affords a yield of 32 % using 0.02 mol % 5b, which is comparable to literature reports at similar catalyst loadings.³² 4-Chlorotoluene does not show appreciable yield of product, and 4-chloroacetophenone only shows low yield at 0.1 mol % precatalyst (Table 3, Entries 7–8). Overall, precatalysts 5a and 5b show comparable catalytic performance for the Heck reaction with a broader substrate scope than similar macrocyclic Pd(II) systems reported in the literature.³⁶ We must note that the performance of 5a and 5b is poor when compared to state-of-the-art Pd C-C coupling systems. State-of-the-art systems currently can afford near complete conversion at catalyst loadings of 100 mol ppm or lower. Additionally, some reports of TOF values are several orders of magnitude greater than those found here.⁷³ Other analogous compounds in the literature also show poor performance compared to state-of-the-art systems.^18,36

The competence of complexes 5a and 5b as precatalysts for C-C bond forming reactions implies that an active molecular catalyst species could be capable of facile cis / trans isomerization of the NHC moieties through intramolecular five-coordinate rearrangement assisted by the pendant amines present in the macrocycle (Scheme 7).⁷⁴

Scheme 7.

cis / trans isomerisation promoted by pendant amine groups via 5-coordinate rearrangement.

The formation of colloidal palladium clusters that serve as a reservoir for the actual catalytic species is common in Pd catalysis.^75–76,77 Douthwaite and co-workers reported the possibility of ligand de-coordination from the metal during a catalytic reaction and concluded that the reaction might be catalyzed by colloidal palladium because they observed an increase in turnover frequency at lower catalyst loading. In this work, 5a and 5b also show an increase in activity at lower catalyst loading, which is a common feature of Pd⁰ catalyzed reactions.³² This observation is inconsistent with the previous report of similar Pd systems,¹⁸ and we infer that loss of ligand from the metal and formation of colloidal Pd is indeed possible. Recent work by Ananikov demonstrates that Pd-based “cocktail systems” in fact contain several dominant catalytic species.⁷⁸ Furthermore, studies have shown that the popular Hg drop test in fact seems to be deficient in distinguishing between possible catalytic species.⁷⁹ Further detailed mechanistic studies are underway and will be reported elsewhere. These Pd systems are our first step into exploring the coordination chemistry and reactivity of these macrocyclic ligands; to combat ligand de-coordination, we plan to explore metals that will favour κ³ and higher coordination numbers for the macrocyclic ligands.

Conclusions

In conclusion, we have synthesized 20-membered macrocyclic bis(NHC)-imidazolium proligands 3a and 3b derived from imidazole and benzimidazole, Ag complexes 4a and 4b, and novel macrocyclic-trans-bis(NHC)Pd(II)Cl₂ complexes 5a and 5b. Interestingly, solid-state samples of 4a and 4b are dimeric and show different coordination environments for the Ag(I)-anionic core of dimeric structures. Ag complexes 4a and 4b were competent transmetalation agents to bis(acetonitrile)-dichloropalladium(II). Complexes 5a and 5b were found to be stable towards air, moisture and heat. The molecular structures of proligand 3a and 3b, Ag carbene complexes 4a and 4b, and macrocyclic-trans-bis(NHC)Pd(II)Cl₂ complexes 5a and 5b were determined by single-crystal X-ray crystallography. 5a and 5b possess a square-planar metal center, and the 20-membered macrocyclic-bis(NHC)-imidazolium/benzimidazolium moiety acts as a bidentate ligand. The coordination modes of the ligand have been observed to consistently be κ² in the solid state and at no point is formation of cationic metal complexes by displacement of an inner-sphere halide observed. Additionally, cis / trans mixtures of the NHC moieties are not observed in the solid state for the Pd systems synthesized. The exploration of the transmetalation behaviour of 4a and 4b with other metals and the resultant coordination geometries of these macrocyclic ligands will be reported elsewhere.

The macrocyclic-trans-bis(NHC)palladium(II) complexes 5a and 5b were demonstrated to be active precatalysts for Heck and Suzuki cross-coupling reactions. Unactivated aryl-Cl bonds can undergo Suzuki coupling in modest yield by 5a. Notably, we observed near quantitative yield for Suzuki coupling of the activated substrate 4-chloroacetophenone catalyzed by 5b. This result is comparable to state-of-the-art catalyst systems capable of coupling aryl-Cl bonds, which are generally considered to be less reactive than heavier aryl halides.⁸⁰ We have shown that complexes 5a and 5b can catalyze Suzuki and Heck coupling reactions in the presence of the steric bulk of our macrocyclic ligands encompassing the Pd center. Although our catalysts are not as active as current state-of-the-art Pd coupling systems, our results show improved yield at shorter reaction times compared to macrocyclic and analogous Pd compounds in the literature.^36,18

Experimental Methods

General Procedures

Oxygen- and water-sensitive reactions and manipulations were performed using glove box and Schlenk techniques under nitrogen atmosphere. All solvents were purchased anhydrous and were stored over molecular sieves in the glove box. All reagents were used as supplied (Aldrich). [PdCl₂(MeCN)₂] was prepared⁸¹ using the literature procedure. High-resolution mass spectra were recorded using a Bruker APEX-II FTMS instrument with an electrospray ionization source. Standard ESI-MS spectra were recorded on a Shimadzu 8040 triple quadrupole-MS system. X-ray crystallographic data were collected on a Bruker APEX CCD-based X-ray diffractometer. ¹H and ¹³C NMR spectra were recorded at probe temperature on 300 MHz and Bruker Avance DPX 400 spectrometers. Chemical shifts are reported in parts per million downfield shift from SiMe₄; coupling constants are reported in Hz. ¹H NMR spectra were referenced internally to the residual proton solvent resonance of CDCl₃ (δ 7.26), CD₂Cl₂ (δ 5.32), DMSO-d₆ (δ 2.50). ¹³C NMR spectra were referenced to CDCl₃ (δ 77.0), CH₂Cl₂ (δ 53.84), DMSO-d₆ (δ 39.51). ¹H COSY, ¹³C HSQC, NOESY experiments were performed using standard Bruker pulse sequences. Microanalysis were performed by Midwest Microlab (Indianapolis, Indiana) or at the University of Rochester CENTC facility where microanalysis samples were weighed with a PerkinElmer Model AD-6 Autobalance and their compositions were determined with a PerkinElmer 2400 Series II Analyzer. Air-sensitive samples were handled in a VAC Atmospheres glovebox at the CENTC facility. Gas chromatography was performed on an Agilent 6890/5973N in positive ion CI mode with a flow rate of 1 mL/min constant flow He, inlet temperature of 250°C, column temperature of 80°C, 20°C/min increase to 250°C (held for 2 min) for a total time of 16 min.

X-ray crystallography

A crystal of suitable shape and dimensions was selected for structural analysis. Intensity data were collected using a diffractometer with a Bruker APEX CCD area detector⁸² and graphite-monochromated radiation. The data were corrected for absorption by the empirical method,⁸³ giving minimum and maximum transmission factors. The space group was determined by systematic absences and statistical tests and was verified by subsequent refinement. The structure was solved by direct methods and was refined by full-matrix least-squares methods⁸⁴ on F². The positions of hydrogens bonded to carbons were initially determined by geometry and were refined using a riding model. Non-hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atom displacement parameters were set to 1.2 times the isotropic equivalent displacement parameters of the bonded atoms. A summary of refinement parameters can be found in Table 4. Further description and details of the refinement of each structure can be found in the supporting information.

Table 4.

Crystal data and structure refinement for silver carbene complexes 4a, 4b, 5a and 5b

	3a	4a	4b	5a	5b
Empirical formula	C34H46Br2Cl6N6	C65H86Ag4Br4Cl2N12	C82H96Ag4Br4Cl4N12	C32H42Cl2N6Pd	C40H46Br0.43Cl1.57N6Pd
Formula weight	911.29	1857.47	2142.62	688.01	807.24
Crystal system	orthorhombic	monoclinic	monoclinic	monoclinic	monoclinic
Space group	Pbca	P21/c	C2/c	P21/c	P21/n
a (Å)	9.350(3)	9.840(4)	31.67(4)	11.612(4)	12.462(17)
b (Å)	16.797(6)	22.482(8)	10.719(17)	8.505(2)	10.751(15)
c (Å)	25.649(8)	15.732(6)	25.17(4)	16.280(5)	14.335(19)
α (deg)	90	90	90	90	90
β (deg)	90	93.172(5)	105.24(2)	94.685(4)	103.665(19)
γ (deg)	90	90	90	90	90
Volume (Å3)	4028(2)	3475(2)	8244(21)	1602.4(8)	1866(4)
Z, Z’	4, 0.5	2, 0.5	4, 0.5	2, 0.5	2, 0.5
Density (calcd) (Mg/m3)	1.503	1.775	1.726	1.426	1.437
Wavelength (Mg/m3)	0.71073	0.71073	0.71073	0.71073	0.71073
Temperature (K)	100(2)	100(2)	100(2)	100(2)	100(2)
F(000)	1856	1844	4272	712	831
Absorption coeff. (mm−1)	2.443	3.536	3.056	0.777	1.107
Absorption correction	Semi-emp. from equiv.	Semi-emp. from equiv.	Semi-emp. from equiv.	Semi-emp. from equiv.	Semi-emp. from equiv.
Max. & min. transmission	0.775 and 0.509	0.869 and 0.373	0.3766 and 0.2313	0.812 and 0.757	0.3782 and 0.2597
θ range/°	1.588 to 27.569	1.581 to 27.723	1.333 to 22.721	1.760 to 27.581	1.950 to 22.722°
Reflection collected	149026	49788	17622	81927	14735
Independent reflection	11335 [R(int)=0.0759]	11151 [R(int)=0.0427]	5545 [R(int)=0.0990]	14455 [R(int)=0.0474]	2508 [R(int)=0.1061]
Data / restraints/param.	11335 / 0 / 218	11151 / 321 / 380	5545 / 588 / 529	14455 / 0 / 189	2508 / 660 / 333
wR(F2 all data)	wR2 = 0.1750	wR2 = 0.1415	wR2 = 0.2256	wR2 = 0.2326	wR2 = 0.2636
R(F obsd. data)	R1 = 0.0597	R1 = 0.0579	R1 = 0.0835	R1 = 0.0751	R1 = 0.0879
Goodness-of-fit on F2	1.006	1.007	1.009	1.004	1.007
Observed data [l>2 σ(l)]	7787	7804	3917	9254	1897
Largest & mean shift / s.u.	0.001, 0.000	0.001, 0.000	0.001, 0.000	0.000, 0.000	0.035, 0.003
Largest diff peak and hole e/Å3	3.282 and −0.783	2.592 and −0.912	1.485 and −1.066	3.153 and −1.415	0.779 and −0.853
τ4				0.000	0.038

wR2 = { Σ [w(Fo2 - Fc2)2] / Σ [w(Fo 2)2] }1/2, R1 = Σ ||Fo| - |Fc|| / Σ |Fo

Synthesis and Characterization of Compounds.

Compounds A, B and 1 were synthesized according to literature procedures.^5,6

N-benzylbis(3-imidazolpropyl)amine (2a).

Imidazole (0.86 g, 12.6 mmol) in THF (10 mL) was added dropwise to NaH (0.30 g, 12.6 mmol) while stirring at ambient temperature. Stirring was continued for 16 hours. To this slurry, N-benzylbis(3-bromopropyl)amine (1.2 g, 3.44 mmol) in THF (10 mL) solution was added, and the resulting solution was stirred for an additional 16 hours. The solution was filtered and the volatile material was removed under reduced pressure to yield N-benzylbis(3-imidazolpropyl)amine as an pale yellow viscous liquid (1.76 g, 95 %). ¹H NMR (CDCl₃): δ 7.37–7.02 (m, 5H of C₆H₅), 7.02 (s, 2H, imi), 6.78 (s, 2H, imi), 3.94 (t, J = 6.72, 4H, -NCH₂), 3.52 (s, 2H, PhCH₂), 2.42 (t, J = 4H), 1.87 (pen, J = 6.72, 4H). ¹³C NMR (CDCl₃): δ 139, 137.1, 129.5, 128.8, 128.5, 127.4, 118.6, 58.7, 50.8, 44.6, 28.6. HR FT-ICR MS calcd for [C₁₉H₂₅N₅+H]: m/z [M+H]⁺: 324.2183; found 324.2803.

N-benzylbis(3-benzimidazolpropyl)amine (2b).

Benzimidazole (0.75 g, 6.30 mmol) in THF (10 mL) was added dropwise to NaH (151 mg, 6.30 mmol) while stirring at ambient temperature. Stirring was continued for 16 hours. To this slurry, N-benzylbis(3-bromopropyl)amine (1 g, 2.86 mmol) was added and the resulting solution was stirred for an additional 16 hours. The solution was filtered, and the volatile material was removed under reduced pressure to yield N-benzylbis(3-benzimidazol-propyl)amine as an colorless viscous liquid (1.13 g, 94 %). ¹H NMR (CDCl₃): δ 7.82–7.78 (ortho, 2H of–CH₂C₆H₅), 7.58 (s, 2H, benzimi-NCHN-), 7.34–7.27 (m, 8H, benzimi and 3H, -CH₂C₆H₅), 4.12 (t, J = 6.8, 4H, -NCH₂), 3.52 (s, 2H, PhCH₂), 2.42 (t, J = 6.4, 4H), 1.87 (pen, J = 6.8, 4H, PhCH₂CH₂CH₂). ¹³C NMR (CDCl₃): δ 144, 143, 139, 133.7, 129, 128.7, 127.6, 122.9, 122.2, 120.6, 109.6, 58.7, 51.2, 43, 27. HR FT-ICR MS calcd for C₂₇H₂₉N₅): m/z [M+H]⁺: 424.2183; found 424.2496.

[L1][Br₂] (3a).

A solution of N-benzylbis(3-imidazolpropyl) amine 2a (1.1 g, 3.4 mmol) and N-benzylbis(3-bromopropyl)amine (1 g, 2.9 mmol) in acetonitrile (200 mL) was refluxed for 48 hours. Removal of the solvent and dissolving in CHCl₃ at −40 °C gave the desired cyclic diimidazolium bromide salt 3a as a white hygroscopic powder in 60 % yield (1.3 g). ¹H NMR (CD₂Cl₂): δ 10.77 (s, 2H of–NCHN-), 7.40–7.32 (m, 10H, -C₆H₅ and 4H, J = 1.5, imi-CH=CH), 4.32 (t, J = 9.20, 8H, -NCH₂), 3.59 (s, 4H, PhCH₂), 2.57 (t, J = 8.8, 8H, PhCH₂CH₂CH₂), 2.18 (pen, J = 9.20, 8H, PhCH₂CH₂CH₂). ¹H NMR (DMSO-d₆): δ 9.20 (s, 2H of–NCHN-), 7.77 (d, 4H, J = 1.5, imi-CH=CH), 7.32 (m, 10H, -C₆H₅), 4.08 (t, J = 6.90, 8H, -NCH₂), 3.51 (s, 4H, PhCH₂), 2.25 (t, J = 6.6, 8H, PhCH₂CH₂CH₂), 1.85 (pen, J = 7.10, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CD₂Cl₂): δ 139, 137, 129.4, 128., 127, 122, 59, 50, 48, 27. HR FT-ICR MS calcd for [C₃₂H₄₄N₆B_r]⁺): m/z [M-Br]⁺: 591.2805; found 591.2803. Calcd for [C₃₂H₄₃N₆]⁺): m/z [M-2Br]⁺: 511.3544; found 511.3546.

[L2][Br₂] (3b).

A solution of N-benzylbis(3-imidazolpropyl)amine 2b (1 g, 2.36 mmol) and N-benzylbis(3-bromopropyl)amine (823 mg, 2.36 mmol) in acetonitrile (120 mL) was refluxed for 24 hours. Concentration of the solution and cooling to −40 °C gave the desired cyclophane bis(NHC) ligand 3b as a white powder in 50 % yield (910 mg). ¹H NMR (CDCl₃): δ 11.31 (s, 2H of–NCHN-), 7.57–7.54 (d, 4H, -CH₂C₆H₅), 7.46 (d, 4H, benzimidazole -C₆H₄), 7.35 (t, J = 7.32, 4H, -CH₂C₆H₅), 7.27 (d, 4H, -CH₂C₆H₅), 4.64 (t, J = 7.2, 8H, benzimidazole -NCH₂), 3.69 (s, 4H, PhCH₂), 2.83 (t, J = 6.4, 8H, PhCH₂CH₂CH₂), 2.65 (pen, J = 7.2, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CDCl₃): δ 144 (–NCHN-), 139.5, 131.7, 129, 128.6, 127, 126, 113, 60.4 (4H, PhCH₂), 51.6, 45.7, 27. HR FT-ICR MS calcd for C₄₀H₄₈BrN₆⁺: m/z [M-Br+H]: 693.3101, 691.3208; found 691.3118, 693.3099. Anal. Found for C₄₀H₄₈Br₂N₆: C 62.33, H 6.21, N 11.052%; Calcd, C 62.18, H 6.26, N 10.88%.

Generation of free carbene in situ (3c).

A grey suspension of sodium hydride (25 mg, 0.037 mmol) in 1 mL of DMSO-d₆ was added to 3a (22 mg, 0.91 mmol) at room temperature. The reaction mixture turned red in color and effervesced immediately. The reaction mixture was stirred for 2 minutes. The reaction mixture was filtered and transferred to a J. Young tube. ¹H NMR (DMSO-d₆): δ 9.20 (s, 2H of–NCHN-), 7.33–7.23 (m, 10H, -C₆H₅), 3.81 (m, 8H, -NCH₂), 3.51 (s, 4H, PhCH₂), 2.27 (m, 8H, PhCH₂CH₂CH₂), 1.71 (m, 8H, PhCH₂CH₂CH₂). ¹³C NMR (DMSO-d₆): δ 208.4, 140.0, 128.5, 128.0, 126.1, 119.0, 58.0, 50.2, 48.0, 28.0.

[(L1)Ag]₂(Ag₂Br₄) (4a).

3a (218 mg, 0.32 mmol) was dissolved in dichloromethane (20 mL), and Ag₂O (150 mg, 0.64 mmol) was added. The reaction vessel was covered with aluminium foil, and the mixture was stirred for 24 hours. The reaction mixture was then filtered through Celite, and the filtrate was dried under reduced pressure to give 4a as a white solid. Yield: 247 mg, 86 %. Crystals suitable for X-ray diffraction studies were grown at room temperature under nitrogen by slow diffusion of pentane into the saturated dichloromethane solution of 4a. ¹H NMR (CD₂Cl₂): δ 7.40 −7.25 (m, 10H, -C₆H₅), 7.05 (s, 4H, imi-CH=CH), 4.25 (t, J = 6, 8H, -NCH₂), 3.63 (s, 4H, PhCH₂), 2.62 (t, J = 5.4, 8H, PhCH₂CH₂CH₂), 1.96 (pen, J = 11.4, 8H, PhCH₂CH₂CH₂). ¹H NMR (CDCl₃): δ 7.36 (m, 10H, -C₆H₅), 7.02 (s, 4H, imi-CH=CH), 4.28 (t, J = 6, 8H, -NCH₂), 3.60 (s, 4H, PhCH₂), 2.60 (t, J = 5.2, 8H, PhCH₂CH₂CH₂), 1.94 (pen, J = 11.4, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CD₂Cl₂): δ 180, 139.7, 129.5, 128.5, 128.3, 126.9, 121.4, 58.2 (PhCH₂N), 48.6, 30.1. ¹³C NMR (CDCl₃): δ 181, 139, 129, 127, 121, 59 (PhCH₂N), 53, 49, 30. ESI-MS calcd for [C₃₂H₄₂AgN₆]⁺): m/z (M-AgBr₂) 617.2516; found 617.2. Calcd for [C₃₂H₄₂N₆+H]⁺: (M-2AgBr+H) 511.3549; found 511.3. Anal. Found for C₃₂H₄₂Ag₂Br₂N_6.: C, 43.09; H, 4.75; N, 9.12%. Calcd for C₃₂H₄₂Ag₂Br₂N₆: C 43.36, H 4.78, N 9.48%.

[(L2)Ag]₂(AgBr₂)₂ (4b).

3b (100 mg, 0.13 mmol) was dissolved in dichloromethane (20 mL), and Ag₂O (60 mg, 0.26 mmol) was added. The reaction vessel was covered with aluminium foil, and the mixture was stirred for 24 hours. The reaction mixture was then filtered through Celite, and the filtrate was dried under reduced pressure to give 4b as a white solid. Yield: 116 mg, 91 %. Crystals suitable for X-ray diffraction studies were grown at room temperature under nitrogen by slow diffusion of pentane into the saturated dichloromethane solution of 4b. ¹H NMR (CD₂Cl₂): 7.50–7.39 (m, 8H, -CH₂C₆H₅ and 8H, benzimidazole -C₆H₄), 7.29 (d, 2H, para-C₆H₅), 4.72 (m, 8H, benzimidazole-NCH₂), 3.72 (s, 4H, PhCH₂), 2.73 (t, J = 4.80, 8H, PhCH₂CH₂CH₂), 2.05 (m, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CD₂Cl₂): δ 181, 144, 140, 134, 129, 128.8, 127, 124, 119, 58.6, 54.3, 46.3, 28.5. HR FT-ICR MS calcd for [C₄₀H₄₆AgN₆]⁺: m/z [M-AgBr₂] 717.2829, 719.2828; found 717.2829, 719.2828. Calcd for [C₄₀H₄₆N₆+H]⁺: m/z (M-2AgBr) 611.3857; found 611.3857. Anal. Found for C₄₀H₄₆Ag₂Br₂N₆(0.6C₅H₁₂): C 50.46, H 4.94, N 8.52%; Calcd, C 50.16, H 5.21, N 8.16%. Analysis was attempted several times and the best analysis obtained matched the above results with solvent remaining in the bulk solid.

trans-bis(NHC)Pd(II)Cl₂ (5a).

Silver carbene 4a (210 mg, 0.237 mmol) was dissolved in dichloromethane (15 mL) and PdCl₂(MeCN)₂ (61.5 mg, 0.237 mmol) was added. The reaction was stirred at 25 °C for 30 minutes and at 60 °C for 20 hours. A pale yellow precipitate formed. The solution was cooled to room temperature and filtered, and the volatiles were removed from the filtrate under reduced pressure to give a white solid. Crude white solid was dissolved in a minimal amount of methylene chloride and excess pentane was added to precipitate the product. The product was isolated by filtration and was washed with excess pentane to give 5a as white solid. Yield: 90 mg, 55 %. Crystals suitable for X-ray diffraction were grown at room temperature under nitrogen by slow vapor diffusion of pentane into a saturated dichloromethane solution of 5a. ¹H NMR (CD₂Cl₂): 7.47 (d, J = 7.6, 4H, ortho-C₆H₅), 7.35 (t, J = 7.6, 4H, meta-C₆H₅), 7.23 (t, J = 7.2, 2H, para-C₆H₅), 6.82 (s, 4H, imidazole–CHCH-), 4.59 (t, J = 5.6, 8H, imidazole-NCH₂), 3.68 (s, 4H, PhCH₂), 3.00 (t, J = 5.6, 8H, PhCH₂CH₂CH₂), 2.18 (t, J = 6, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CD₂Cl₂): δ 170.7, 141, 129, 128.6, 127, 121, 59.8, 33.8, 47.8, 31. HR FT-ICR MS calcd for [C₃₂H₄₂ClN₆Pd]⁺): m/z [M-Cl] 651.2194; found 651.2186. Anal. found for C₃₂H₄₂Cl₂N₆Pdˑ(CH₂Cl₂): C 51.62, H 5.36, N 10.52%;. Calcd, C 51.28, H 5.74, N 10.87 %. Analysis was attempted several times and the best analysis obtained matched the above results with solvent remaining in the bulk solid.

trans-bis(NHC)Pd(II)X₂ (5b).

Silver carbene 4b (150 mg, 0.152 mmol) was dissolved in dichloromethane (10 mL), and PdCl₂(MeCN)₂ (40 mg, 0.155 mmol) was added. The reaction was stirred at 25 °C for 30 minutes and at 60 °C for 20 hours. A pale yellow precipitate formed. The solution was cooled to room temperature and filtered, and the volatiles were removed from the filtrate under reduced pressure and were washed with pentane to give 5b as a white solid. Yield: 72 mg, 58 % based on C₄₀H₄₆N₆PdCl_1.47Br_0.43 (MW = 807.24). Crystals suitable for X-ray diffraction were grown at room temperature under nitrogen by slow vapor diffusion of pentane into a saturated dichloromethane solution of 5b. ¹H NMR (CD₂Cl₂): δ 7.56 −7.25 (m, aromatic 18H, -C₆H₅ and 4H, imi-CH=CH), 5.02 (bs, 8H, benzimidazole-NCH₂), 3.76 (s, 4H, PhCH₂), 3.09 (bs, 8H, PhCH₂CH₂CH₂), 2.18 (t, J = 5.6, 8H, PhCH₂CH₂CH₂). ¹³C NMR (CD₂Cl₂): δ 182.6, 141.2, 134.8, 128.9, 128.7, 127, 123, 110, 59, 44.5, 30.1, 28.7. HR FT-ICR MS calcd for [C₄₀H₄₆Cl₂N₆Pd]⁺): m/z [M-Cl] 751.2507; found 751.2518. Anal. found for C₄₀H₄₆Cl_1.57Br_0.43N₆Pdˑ(CH₂Cl₂): C 55.19, H 5.42, N 9.42%; Calcd, C 55.39, H 5.47, N 9.40%. Analysis was attempted several times and the best analysis obtained matched the above results with solvent remaining in the bulk solid.

General procedure for Suzuki coupling reactions.

A 15 mL Teflon-sealed pressure tube with a magnetic stir bar was charged with aryl halide (0.2 mmol), phenylboronic acid (36 mg, 0.45 mmol), cesium carbonate (196 mg, 0.90 mmol), and 1,3,5-trimethoxybenzene (20–30 mg) as an internal standard. Then, 1,4-dioxane (1.50 mL) and a solution of the precatalyst in CH₂Cl₂ (0.1 mol %, 50 μL, 0.04 M) were added in the glove box. The reaction mixture was heated to 100 °C in an oil bath with vigorous stirring. The reaction mixture was filtered through a short pad of SiO₂, and the filtrate was analyzed by GC and ¹H NMR.

General procedure for Heck coupling reactions.

A 15 mL Teflon-sealed pressure tube with a magnetic stir bar was charged with aryl halide (0.20 mmol), n-butyl acrylate (51.3 mg, 0.40 mmol), n-butyl ammonium bromide (6.5 mg, 0.02 mmol), and 1,3,5-trimethoxybenzene (20–30 mg) as an internal standard. A solution of precatalyst (0.02 mol %, 50 μL, 4 mM solution) in CH₂Cl₂ was added in the glove box. Anhydrous Na₂CO₃ (24 mg, 0.23 mmol) and N,N-dimethylacetamide (2 mL) were added, and the tube was flushed with N₂. The reaction mixture was heated in an oil bath at 140 °C for the desired time period. The reaction mixture was cooled and filtered through a short pad of SiO₂. The filtrate was analyzed by ¹H NMR.