Invisible Chelating Effect Exhibited between Carbodicarbene and

Article Cite This: Organometallics XXXX, XXX, XXX-XXX

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Invisible Chelating Effect Exhibited between Carbodicarbene and Phosphine through π−π Interaction and Implication in the CrossCoupling Reaction Wei-Chih Shih,† Yun-Ting Chiang,†,‡ Qing Wang,§ Ming-Chun Wu,† Glenn P. A. Yap,∥ Lili Zhao,*,§ and Tiow-Gan Ong*,†,‡ §

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, People’s Republic of China † Institute of Chemistry, Academia Sinica, Nangang, Taipei, Taiwan, Republic of China ‡ The Department of Applied Chemistry, National Chiao Tung University, Hsin-chu, Taiwan, Republic of China ∥ The Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States S Supporting Information *

ABSTRACT: Palladium complexes supported with the mixed ligands carbodicarbene (CDC) and different phosphine ligands (PPh3, PTol3, and PCy3) were prepared, and their molecular structures were characterized. Examination of the structures of 2-PPh3 and 2-PTol3 with cis configuration discloses the existence of an unexpected π−π interaction between one phenyl group of the phosphine and the benzimidazole ring of a CDC. The palladium complex 2PPh3 is an active Suzuki−Miyaura catalyst with a wide scope of substrates containing various functional groups and steric demands. In contrast to electron-withdrawing aryl bromide, the yield of product for electron-rich substrates was improved by adding a catalytic amount of DMSO under aerobic conditions. The solution NMR and structural analysis has revealed that the intramolecular π−π interaction between CDC and phosphine ligands has a positive influence on the activity of the reaction, which is further supported by quantum chemical calculations.

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INTRODUCTION The remarkable discovery of N-heterocyclic carbenes (NHCs) as neutral σ-donating ligand platforms prompted a massive breakthrough in homogeneous transition-metal catalysis.1 In addition to the broadly explored NHCs, recent efforts toward discovering a stable unique carbon species has also yielded carbodicarbenes (CDCs) or carbones,2 featuring a dicoordinated central carbon(0) atom bearing two electron lone pairs. Because of these two electron lone pairs, CDCs show a far stronger σ-donor strength in comparison to NHC ligands. For instance, our group recently isolated a highly electron deficient dicationic boron complex supported by a CDC framework,3 a demonstrative case where similar stabilization could not be achieved by normal NHC ligands. In addition, our group and those of Meek and Stephan have independently established CDCs as useful ligands for many catalytic transformations.4 Nonetheless, it is clear that much remains to be done in order to understand the topological properties of CDCs and their potential in catalysis. Although a monoligand framework has been always dominated the realm of transition-metal catalysis, mixed ligand systems have occasionally appeared as a complementary strategy to facilitate the efficiency of the reaction. The synergistic effect invoked by cooperative effects between two © XXXX American Chemical Society

ligands may improve the stability of an active species and prolong the life span or increase the turnover number of the catalyst in the reaction. An olefin metathesis catalyst based on the Grubbs second-generation ruthenium complexes bearing a mixed NHC and phosphine framework is living proof of employing a mixed ligand strategy to improve thermal and functional robustness as well as activity of the catalysts.5 Other related prominent examples that have relied on a mixed ligand concept can also be witnessed in the recent development of a Pd-mediated C−C and C−N catalytic cross-coupling reaction, the so-called PEPPSI-NHC catalyst (pyridine, enhanced, precatalyst, preparation, stabilization, and initiation).6 Previously, our group has focused efforts on developing synthetic methods of expanding the structural diversity of CDC scaffolds.7 Despite the ever-increasing utility of strongly σ donating ligands, a CDC, with two lone pairs of electrons, has no spare orbital (or LUMO with sufficient low energy) for possible π back-bonding from low-oxidation-state metal centers.2 Definitely, a low affinity of the CDC for an electron-rich metal complex would have detrimental consequences toward engineering a more robust and resilient Received: September 10, 2017

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DOI: 10.1021/acs.organomet.7b00692 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 1. Synthesis of Mixed Ligand Pd(II) Complexes

Figure 1. Molecular structures of Pd complexes 2-PPh3 (left), 2-PTol3 (center), and 2-PCy3 (right) with thermal ellipsoids drawn at the 30% probability level. There are two unique asymmetric structures in 2-Tol3, but only one of the units is used for the representative drawing. All hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): 2-PPh3, Pd−Cl(1) 2.3679(6), Pd−Cl(2) 2.3733(6), Pd−C(1) 2.063(2), Pd−P(1) 2.2503(6), C(1)−C(2) 1.383(3), C(1)−C(11) 1.409(3), C(2)−C(1)−C(11) 115.63(19), P(1)−Pd−C(1) 96.35(6); 2-Tol3, Pd(1)−P(1) 2.261(1), Pd(1)−Cl(1) 2.383(1), Pd(1)−Cl(2) 2.367(2), Pd(1)−C(1) 2.049(4), C(1)−C(2) 1.374(7), C(1)−C(11) 1.412(8), C(11)−C(1)− C(2) 117.7(4), Pd(1)−C(1)−C(2) 126.3(4), Pd(1)−C(1)−C(11) 114.0(4), C(1)−C(2)−N(1) 128.5(5), C(1)−C(2)−N(2) 125.4(5), N(1)− C(2)−N(2) 106.1(4), C(1)−C(11)−N(3) 125.5(5), C(1)−C(11)−N(4) 127.5(5), N(3)−C(11)−N(4) 106.7(4); 2-PCy3, Pd(1)−P(1) 2.3385(7), Pd(1)−Cl(1) 2.3245(7), Pd(1)−Cl(2) 2.3107(8), Pd(1)−C(1) 2.111(2), C(1)−C(2) 1.343(3), C(1)−C(11) 1.415(4), C(11)−C(1)−C(2) 123.6(2), Pd(1)−C(1)−C(2) 124.1(2), Pd(1)−C(1)−C(11) 112.3(2), C(1)−C(2)−N(1) 127.6(2), C(1)−C(2)−N(2) 128.2(2), N(1)−C(2)− N(2) 104.1(2), C(1)−C(11)−N(3) 126.7(2), C(1)−C(11)−N(4) 125.7(2), N(3)−C(11)−N(4) 107.3(2).

palladium complex. Such a unique interaction accounts for an invisible and bridging linkage between these two ligands, enforcing cisoid conformation in the complex and exerting a certain degree of positive influence on the coupling activity, which is unprecedented so far. Herein we wish to present our comprehensive studies on the synthesis and structural characterization of a series of [(CDC)(PR3)PdCl2] complexes, which act as precatalysts in the carbon−carbon cross-coupling reaction. We also show how these two ligands are working in a dynamic manner and identify the chemical principles that govern how carbodicarbene-based complex systems promoted the sterically hindered coupling process.

ligated catalytic species in molecular reactions. To facilitate the use of carbodicarbene in reactions, we envisaged a metal complex possessing mixed ligands of CDC and phosphine with dual functional tasks. Through a strong σ-dative bonding, a CDC scaffold would facilitate the reactivity of a high-oxidationstate metal in the catalytic cycle. At the same time, the PPh3 ligand with a LUMO orbital for π back-bonding would modulate the reaction, as the metal complex cycled back into a lower oxidation mode. In line with our strategy, we have elected the palladium-mediated Suzuki−Miyaura cross-coupling reaction as our model of study to examine the efficacy and to obtain mechanistic insight. During the course of our study, we serendipitously discovered an unexpected intramolecular π−π interaction between a CDC and phosphine ligands within the B


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Organometallics

Figure 2. Variable-temperature 1H NMR spectra of 2-PPh3 complexes in the range of δ 6−9 ppm and in the temperature range between 210 and 330 K.

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RESULTS AND DISCUSSION Synthesis and Structure Characterization. Expanding upon our recent success in diversifying the library of CDCs, we set out to prepare a number of CDC palladium complexes with several different phosphine ligands. In order to take advantage of its NMR simplicity in characterization, we chose the unsymmetrical scaffold 1 as the CDC ligand target in our investigative efforts (Scheme 1). The preparation of the CDC 1 can be achieved in a good yield via the SN2 reaction of an Nheterocyclic olefin adduct with thioether developed recently by our group.7 We succeeded in preparing the palladium complexes 2-PPh3 and 2-PTol3 by the reactions of CDC 1 with the corresponding PdCl2(PAr3)2 complexes8 in THF solution at ambient temperature. The blue crude solid product can be further purified and isolated in satisfactory yield (∼80%) with a THF treatment to wash off excess phosphine. The 1H NMR of 2-PPh3 is notably distinct from that of its original CDC ligand 1 with two new methyl signals at δ 4.51 and 2.18 ppm and four other notable isopropyl doublets at δ 2.14, 1.53, 1.17, and 1.11 ppm. These NMR patterns clearly reflect an unsymmetrical environment in the palladium coordination sphere. Crystals of 2-PPh3 suitable for an X-ray diffraction experiment were grown from a concentrated CH2Cl2 solution layered with hexane at laboratory temperature. This compound crystallized in the triclinic space group P1̅. The molecular structure of 2-PPh3 (see Figure 1, left) unambiguously adopts an imperfect square-planar palladium geometry with two chlorides arranged in a cis manner. The C(1)−Pd−P(1) angle is 96.35(6)°, larger than the ideal 90° to avoid unfavorable steric interactions with the CDC ligand. The Pd−carbone bond distance is about 2.063(2) Å, which is slightly shorter than that for the (CDC)Pd(η3-allyl)Cl complex (2.10 Å) previously reported by our group,2d indicating a robust σ-dative Pd←C bond. As expected, the trans influence of PPh3 and carbodicarbene leads to a lengthening effect on the Pd−Cl bond distances (2.3732(5) and 2.3679(6) Å, respectively).9 Alternatively, we also established compound 2-

PTol3 as a cis square-planar complex (Figure 1, center), and most structural parameters are relatively comparable to those of 2-PPh3, warranting no further comment. π−π Interaction between PPh3 and Carbodicarbene Ligands. Of particular interest, both 2-PPh3 and 2-PTol3 have adopted an unexpected cis arrangement, considering that most known mixed ligand [(NHC)(PR3)PdX2] complexes embrace a trans configuration to minimize unnecessary high-energy steric hindrance within the coordination environment.10 Close examination of the structures of 2-PPh3 and 2-PTol3 disclosed that an unexpected π−π interaction existed between one of the phenyl groups of the phosphine and the benzimidazole ring of the CDC with estimated centroid−centroid distances of 3.25 and 3.30 Å, respectively. Small dihedral angles of 4.62° (2PPh3) and 5.93° (2-PTol3) between least-squares planes confirmed the presence of parallel intramolecular π−π stacking, which indeed is more like a face to face or sandwich pattern.11 Such an unexpected intramolecular stacking π interaction has perhaps promoted 2-PPh3 and 2-PTol3 to adopt a cis geometry. Few studies of the influence of π stacking on olefin metathesis reactions have been reported on NHC-based Grubbs ruthenium catalysts, and these have concerned intramolecular noncovalent interactions between NHC and the benzylidene moiety.12 To the best of our knowledge, no report so far has mentioned or identified structures with intramolecular π−π stacking between an NHC and phosphine within a coordination complex. In this context, the intraligand π−π stacking may serve as an invisible bridging linkage for a chelating effect, which would exert a certain degree of influence on the catalytic reaction. To gain more insight into the role of intramolecular π−π stacking, we synthesized the CDC palladium complex 2-PCy3 bearing a phosphine ligand containing no aryl moiety. In the absence of a collaborative π−π connection, the structure of 2PCy3 embraces a trans conformation to avoid unfavorable steric interactions arising from the close proximity between ligands (the cone angle of PCy3 is 170°).13 Interestingly, the trans effect invoked by PCy3 led to an elongated Pd−CDC bond C


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Organometallics distance, while the Pd−Cl bond lengths have been shortened to 2.324 and 2.311 Å in comparison to 2-PPh3 and 2-PTol3. Certainly the structural evidence indicating the π−π interaction between CDC and phosphine in 2-PPh3 and 2PTol3 could be due to the crystal packing or alignment of the molecular units in the solid state. We were curious if a specific nonbonding intramolecular interaction is still effective in a more environmentally dynamic solution. Thus, we have employed proton NMR to probe this possibility in solution (Figure 2). In principle, the cis isomer has lower symmetry in comparison to the trans isomer. This geometric phenomenon has been exemplified by the case of cis-2-PPh3, with two chemically distinct NMR signals arising from the methyl pendant arms of CDC (δ 4.51 and 2.18 ppm) at ambient temperature, while trans-2-PCy3 possesses only a single methyl peak at δ 3.71 ppm. We postulated that increasing the solution temperature of 2-PPh3 might break the π−π interaction that holds the CDC and phosphine ligand together in a cis configuration, and isomerization might occur in the solution state with detection of the trans analogue. Increasing the solution temperature to 60 °C did not seem to affect the geometry of 2-PPh3, as it showed no change in chemical shift or peak pattern distribution for the methyl and isopropyl groups. When the proton NMR of 2-PPh3 was monitored at a colder temperature of −63 °C, we unexpectedly observed two new triplet peaks located at 8.25 and 8.40 ppm accompanied by multiple broad upfield peaks ranging from 6.50 to 6.80 ppm. Because of a slow rotation of the phosphine ligand around the Pd−P bond at low temperature, we attributed these two triplet signals at 8.25 and 8.40 ppm to m-C−H moieties residing at two aryl groups of PPh3 that are far away from the CDC ring. On the other hand, multiple broad peaks at 6.50−6.80 ppm are thought to be related to the other aryl group of the phosphine close to the CDC ring for more effective π−π interaction, triggering an unorthodox upfield shift in aromatic signals resulting from the shielding effect of the CDC ring. An upfield chemical shift for acceptor nuclei resulting from the ring current effect between both aromatic rings has been reported previously.14 Unambiguous peak identification of the PPh3 derived from characteristic upfield-shifted signals (π−π interaction) and two triplet signals (non-π−π interaction) was further ascertained by results from 1H−1H−COSY (see the Supporting Information for further details). In short, we confidently believe that the intramolecular π−π interaction does exist within the molecules of 2-PPh3 complexes in the solution state, which is important in enforcing the cis configuration of 2-PPh3. This is supported by quantum chemical calculations at the RI-BP86+(D3BJ)/def2-SVP level of theory (see the Supporting Information for computational details). As shown in Figure 3a, the optimized structure of cis-2PPh3 is in excellent agreement with the experimental structure. The calculated distance of the intramolecular π−π interaction of 3.215 Å was in line with experimental value of 3.25 Å, which accounted for the stability of the cis isomer by 9.9 kcal/mol relative to the trans form (see the Supporting Information for the optimized geometry of the trans isomer). Catalytic Reaction in Carbon−Carbon Cross-Coupling Process. Several decades have witnessed a large number of NHC-promoted metal-mediated homogeneous catalyses. Regrettably, research activities focused on carbodicarbene-led metallic catalysis are still lacking. In comparison to the wellestablished NHCs and CAACs, carbodicarbene or carbone features powerful σ donation but no vacant orbital for π back-

Figure 3. Optimized structures of (a) PPh3[CDC]PdIICl2 and (b) PPh3[CDC]Pd0 6 at the RI-BP86+(D3BJ)/def2-SVP level of theory. Key bond distances and bond angles are given in angstroms and degrees, respectively. Trivial hydrogen atoms have been omitted for clarity. Color code: Pd, dark green; P, orange; N, blue; C, gray; H, white.

bonding at the central carbon of the carbone. Obviously, such a subtle electronic topology of the carbodicarbene would have a dramatic influence on the catalytic reaction; thus, understanding the catalytic behavior is essential to stimulate novel and exciting applications akin to those for NHCs and CAACs. To this end, we have selected the traditional Suzuki−Miyaura carbon−carbon cross-coupling reaction for this purpose. To examine the viability of the C−C cross-coupling reaction (Table 1), we attempted the reaction using 4′-bromoacetophenone (3a) and phenylboronic acid (4a) at 130 °C in toluene with 3.5 mol % of 2-PPh3 in the presence of K3PO4 (2.8 equiv). To our delight, the expected cross-coupling product (5aa) was obtained in 62% yield (entry 1). The efficacy of the reaction could be further improved to higher yields of 83% and 90% by changing the base to Cs2CO3 and CsOAc (entries 2 and 3). Changing the reaction solvent to DME with a slightly lower reaction temperature (100 °C) allowed for the yield to be maintained in a range of ∼90% (entries 7 and 8) using the cesium base. Increasing the reaction temperature to 160 °C in DMF solution had a dampening effect on the yield of the reaction (23%, entry 5), presumably due to the instability of the catalyst at higher temperatures. Other solvents such as THF, dioxane, and DMSO were also examined and found to be less suitable in this catalytic reaction. Palladium complexes such as 2-PTol3 and 2-PCy3 (entries 11− 14) appear to be less effective than 2-PPh3, despite several attempts to optimize the reactions under various conditions. In spite of the slightly higher yield of reaction using CsOAc, the Cs2CO3 reagent was selected as the choice of base in subsequent reaction scope investigations, because it is chemically benign to substrates bearing sensitive functional groups. With the optimization conditions in hand (entry 1, Table 2), we examined the reaction scope with various boronic acids (4y, black) with 4′-bromoacetophenone (3a, blue) (entries 1−7). Excellent yields were observed for methyl substituents at different positions of the arylboronic acid (4b−d, entry 2). Arylboronic acids bearing sterically bulky tert-butyl and vinyl functional groups afforded the corresponding cross-coupling products 5ae (92%) and 5af (67%) in surprisingly good yields. D


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Mechanistic Considerations. There is lack of detail and systematic mechanistic investigation concerning the role of carbodicarbene in promoting C−C cross-coupling reactions. Therefore, a systematic mechanistic probe would be advantageous for the future development of carbodicarbene in catalysis. In this study, we want to illuminate and understand the CDCsupported carbon−carbon cross coupling reaction on (a) the discrepancy of this reaction with electronically different substrates and (b) the high reactivity for sterically demanding substrates assisted by intermolecular π−π interactions within the metal complexes. During the course of catalytic cross-coupling studies, we noticed a low efficiency of the reaction upon using electron-rich aryl bromides (Scheme 2-1, entry 1) under N2. Nonetheless, the yield of this reaction could be increased dramatically to 65% (1.3 equiv of boronic ester) and 80% (1.5 equiv of boronic ester) under aerobic conditions and with the addition of DMSO. These results are at odds with the experimental outcomes (Scheme 2-2) generated by 3a, as witnessed in its reaction yield of 64% under N2 and 60% in air in 1 h reaction time. At this juncture, we performed intermolecular competition experiments by using equimolar amounts of 3a and 3i under the standard conditions in the same reaction flask (Scheme 2-3). The reaction was complete within 2.5 h to afford 71% of 5aa and 8% of 5ia, suggesting that the stability of Pd(0) prior to the oxidative addition step is a plausible cause for such a divergent reactivity for dissimilar electronic substrates. These discrepancies in catalytic outcomes between electronwithdrawing and -donating substituents has raised a critical question as to whether the CDC-supported catalyst is a true homogeneous catalyst or, as discussed previously, that some of the palladium-mediated cross-coupling reaction is heterogeneous.16 We performed a mercury test, a well-known catalyst poison for heterogeneous reactions, in order to address the nature of the reaction.17 The carbon−carbon cross-coupling experiment with 2-PPh3 under similar catalytic conditions was stirred with a large excess amount of Hg (∼0.175 g, 50 equiv) (Scheme 2-4). A partial inhibition by Hg(0) was observed, as the catalytic efficiency has been diminished to 56% from its original yield of 88%. Furthermore, we also found that increasing the amount of Hg(0) to 150 equiv did not completely suppress the catalysis, which managed successfully to maintain a catalytic activity in the range of 44% conversion. The results of the mercury test illustrated that the residual catalytic activity may arise from continued generation of the remaining active homogeneous catalysts. At the same time, we also attributed the reduced catalytic activity to instability of a Pd(0) species, which would slowly decompose to palladium particles prior to the occurrence of facile oxidative addition, particularly electron-rich aryl bromide. We reasoned that the Pd(0) species possesses a comparatively weaker affinity for carbodicarbene ligand, which lacked a lower-lying π* orbital to facilitate possible back-bonding that might occur from an electron-rich Pd(0) center. In the case of 3i, the oxidative addition step of electron-rich aryl bromide is not sufficiently fast enough, leading to decomposition of the active species and hence to lower conversion under an N2 atmosphere. Consistent with our hypothesis for the rapid decomposition of Pd(0) with electron-rich substrates, we note that adding DMSO and carrying out the reactions in the presence of oxygen would in fact improve the yield of the reaction. We attribute this to DMSO facilitating the reoxidation of Pd(0) to Pd(II) under

Table 1. Optimization Process

entry 1 2 3 4 5 6 7 8 9d 10d

2-x

2-PPh3

basec

solvent

T (°C)

yieldb (%)

K3PO4 Cs2CO3 CsOAc CsOAc CsOAc CsOAc CsOAc Cs2CO3 Cs2CO3 Cs2CO3

toluene toluene toluene THF DMF dioxane DME DME EtOH DMSO

130 130 130 100 160 120 100 100 80 100

62 83 90 28 23 NR. 93 86 82 17

11 12

2-PTol3

CsOAc Cs2CO3

DME DME

100 100

37 43, 76d

13 14

2-PCy3

CsOAc Cs2CO3

DME DME

100 100

26 69d

a Unless specified otherwise, reactions were carried out with aryl bromide 3a (1 mmol), arylboronic acid 4a (1.3 mmol), base (2.67 mmol), and Pd catalyst 2-X (3.5 mol %) in a selected solvent under N2 for 2.5 h. bDetermined by 1H NMR spectroscopy using 1,3,5trimethoxybenzene as an internal standard. c2.67 equiv of base (except for Cs2CO3) was used. 2.5 equiv was added when Cs2CO3 was used as base. dIn air.

Electron-deficient substrates bearing CN (4g) and NO2 (4h) groups were also examined and found to have high conversions (entries 5 and 6). An arylboronic acid bearing an electrondonating methoxy moiety (4i) was also a suitable coupling reagent for electron-withdrawing aryl bromide (3a) and neutral aryl bromide (3b). Subsequently, we examined the viability of the Suzuki−Miyaura cross coupling reaction of phenylboronic acid (4a) with various aryl bromide derivatives (Table 2, entries 9−14). Encouraged by these results, we tested the effect of substitutions on the aryl bromide and found that both electron-donating and-withdrawing substituents did not affect the efficiency (3b−h). It is worth noting that a catalytic amount of DMSO additive in methylphenyl bromide in air is required to guarantee high yields for the formation of 5ba−da (entry 9; vide inf ra for subsequent explanation). To our surprise, this method is also capable of streamlining products 5ia (Table 2, entry 14) and 5ja (entry 17) possessing the hydroxyl moiety in satisfactory yield. Finally, we also successfully performed a cross experiment to permute two different electronic environments for aryl bromide and boronic acid (entries 15 and 16), demonstrating the flexibility of this reaction procedure. To further demonstrate the capability of the catalyst, we have tested several more challenging substrates, as illustrated in Table 3. High efficiency in cross coupling for the sterically crowded mesityl and 9-phenanthrene boronic ester with aryl bromide 3a can be achieved to afford 5ak,al, respectively. Similarly, representative sterically challenging coupling products such as 5ka,kp,qp,mb were also obtained in good yield by switching to relatively bulky aryl bromide derivatives. Finally, this method is also appropriate for constructing π-extended compounds useful for possible photomaterial applications, exemplified by the formation of 5op,tg,rs.15 E


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Organometallics Table 2. Scope of Cross-Coupling Reactiona

a

Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), and Pd catalyst 2-PPh3 (3.5 mol %) in DME at 100 °C under N2 for 2.5 h. bIsolated yield. cDMSO 12.8 mol % was added. dIn air.

Table 3. Scope of Sterically Challenging Substratesa,b

a

Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), Pd catalyst 2-PPh3 (3.5 mol %), and DMSO (5 mg) in DME at 100 °C under N2 for 2.5 h. bIsolated yield. cReaction without DMSO.

F


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Organometallics Scheme 2. Selected Reactions for Mechanistic Studya,b

a

Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), and 2-PPh3 (3.5 mol %) in DME at 100 °C except for those with additional notation. bThe above yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. cIsolated yield.

far in any cross-coupling reaction studies employing a mixed ligand system. Interestingly, Peris and co-workers have demonstrated how homogeneous catalysts with polyaromatic functionalities of the NHC possess properties that clearly differ from those of analogues without π−π interactions.20 The results in Table 1 showed clearly that trans-2-PCy3 was a less effective catalyst than its counterparts 2-PPh3 and 2-Tol3, clearly hinting that the intramolecular π−π interaction plays a secondary role in the catalytic reaction. At this point, we could not rule out the possibility that sterics also played some role in that respect. We believe that this unique π−π interaction between ligands may function as an invisible and weak bridging linkage between these two ligands, enforcing cisoid conformation in the complex. Moreover, we speculated that the geometric structure invoked by π−π interaction should exert a certain degree of positive influence on (i) the coupling activity, especially with sterically demanding substrates, and (ii) their persistent stability in the catalytic turnover. First, the role of π−π interactions is supported by the fact that 2-PPh3 is capable of delivering the sterically hindered and polyaromatic coupling product in excellent yield. To understand the phenomena, we conducted another intermolecular competition reaction between 3q and 3k with arylboronic ester 4p (Scheme 4-2) under our standard conditions, which provided almost equal yields of both aryl bromides, as demonstrated previously in Table 3. To our surprise, the more sterically crowded 3q (66%) has reacted preferentially in comparison to 3k (33%). This observation provides a possible clue that intramolecular π−π interactions reinforced the cis configuration of the metal complex to create a larger space to fit the incoming substrate with large steric functional substituents. At the same time, the π−π interaction force between ligands has also aided a more

aerobic conditions and thus minimizing the competitive formation of inactive palladium particles.18 Taking together all of these outcomes and the available literature, we propose in Scheme 3 that two catalytic cycles are involved in the carbodicarbene palladium complex catalysis for the carbon−carbon cross-coupling reaction. In a cross-coupling cycle, 2-PPh3 is transformed into the active dicoordinated palladium(0) species 6 by reduction, which should undergo oxidative addition more easily with an aryl bromide bearing an electron-withdrawing group to afford palladium(II) complex 7. Transmetalation of arylboronic ester occurred to generate 8 followed by a reductive elimination process, affording 5, the cross-coupling product. In the catalyst regeneration cycle, the active species 6 could also be in equilibrium with the palladium(0) species 9 assisted by DMSO as a resting state and serving as a catalyst reservoir (step E). Complex 9 reacted with O2 to yield the peroxo complex 10, eventually leading to hydroxy complexes 11 in the presence of a trace amount of H2O. An NHC palladium peroxo complex like 10 has been isolated and fully characterized.19 An excess of the arylboronic acid was added to complex 11, reducing it back to Pd(0) 6. Such a proposed notion is consistent with the single individual experiment demonstrated in Scheme 4-1, where 2-PPh3 could promote homocoupling of arylboronic acid 3i to furnish 5ii under aerobic conditions. The second intriguing aspect of this catalytic reaction is that the CDC-supported cross-coupling reaction is capable of promoting reactions with sterically hindered substrates. In light of the solid structural and solution NMR evidence, we were curious if the intramolecular π−π interaction between CDC and phosphine ligands within the palladium complex played any critical role in catalysis, which is undocumented so G


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Organometallics Scheme 3. Proposed Mechanisma

a

Legend: (A) oxidative addition; (B) transmetalation; (C) reductive elimination; (D) irreversible formation of palladium black; (E) DMSO coordination; (F) oxidation; (G) H2O reaction; (H) transmetalation via boronic ester; (I) reductive elimination.

Scheme 4. Selected Experiments

rapid reductive elimination process through a more rigid cis configuration. This beneficial effect resulting from π−π interactions was further verified, as no cross-coupling reaction was observed from a blank reaction of 3k and 4p mediated by the CDC-free complex (PPh3)2PdCl2·21 To gain insight into the reaction mechanism, we conducted a detailed computational mechanistic study for the cross-coupling reaction of aryl bromide 3a and phenylboronic acid 4a mediated by the active species PPh3[CDC]Pd0 6 (see Figure 4). In the initial stage, aryl bromide 3a approached the coordinatively unsaturated complex 6, generating the weakly bonded intermediate im-A that was exothermic by 15.1 kcal/

mol. Subsequently, the oxidative addition step proceeded through a transition state (TS-A) with a free energy barrier of 11.3 kcal/mol to generate the intermediate PPh3[CDC]PdII(Ar)Br 7, which is relatively more stable (40 kcal/mol) in comparison to its starting material of 3a + 6. The energy barrier for the transmetalation step 7 → 8 via the transition state TS-B was observed to be abnormally high, 40.4 kcal/mol with respect to the former intermediate 7. However, it is well known that the ideal gas-phase model intrinsically overestimates the entropic contributions, especially in the presence of multiple components in the reaction. For example, a reaction containing m to n components has an additional free energy correction of H


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Figure 4. Calculated energy profile at the RI-BP86+(D3BJ)/def2-SVP level for the cross-coupling reaction of aryl bromide and boronic acid mediated by 2-PPh3. Key bond distances and bond angles are given in angstroms and degrees, respectively. Trivial hydrogen atoms have been omitted for clarity. Color code: Pd, dark green; P, orange; N, blue; C, gray; H, white.

(m − n) × 4.3 kcal/mol.22 Alternatively, a scaling factor of 0.5 to the entropic contributions should be applied as a rough estimation on the basis of the experimental observations.23 On the basis of overestimated entropy penalty, the barrier for the transmetalation step should be reduced to ca. 31 kcal/mol. Clearly, even the corrected value in the transmetalation step is still slightly higher for the proposed mechanism to be energetically feasible under ambient conditions. However, the value agrees well with the reaction performed at high temperature (>100 °C). In the final step of the reaction pathway, the reductive elimination process proceeds smoothly to regenerate the active species 6 with a free energy barrier of 9.1 kcal/mol, which is the smallest activation energy in the whole calculated reaction pathway. These computational findings clearly support the notion that the cis conformation enforced by the π−π interaction within the complex encouraged the facile reductive elimination process for sterically demanding substrates. The overall reaction from 3a + 4a leading to 5a is moderately exothermic by 21.1 kca/mol, which provides a driving force for this reaction. Our calculations provide firm support to the hypothesis that the strong intramolecular π−π stacking interactions (i.e., the red dashed lines), with average distances between 3.2 and 3.7 Å, play a very important role in stabilizing the transition states and intermediates during the whole catalysis. At the equilibrium step of E in the catalyst regeneration cycle, we were curious whether the π−π stacking persisted in Pd(0) complex 6 with a linear geometry. As illustrated in Figure 3b by the theoretical calculations, the calculated structure of 6 is bent slightly from linearity with a P−Pd−C(1) angle of

159.9°. The Pd−C(1) bond length of 2.074 Å is marginally longer than that in 2-PPh3 (2.063 Å), while the Pd−P bond length of 2.223 Å is slightly shorter than 2.25 Å, showing that the bonding contribution of phosphine ligand is much more significant than that of the CDC for palladium in a low oxidation state. In addition, we also saw no evidence of π−π interaction, as the phenyl group in PPh3 was no longer parallel with the benzimidazole ring of CDC ligand. Nonetheless, the weak agostic interaction (Pd- - -H(1) (2.526 Å) and Pd- - -H(2) (2.082 Å)) from the Me and iPr ligands in CDC played an essential role in stabilizing the Pd(0) intermediate as well as holding the weakly coordinated CDC from being completely dissociated away from the metal center. Again, this computational finding is consistent with the notion that the low reactivity of electron-rich aryl bromide under an N2 atmosphere is due to the instability of complex 6, as discussed earlier in our first part of mechanistic studies.

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CONCLUSION In summary, we have successfully prepared and characterized palladium complexes containing carbodicarbene mixed with different phosphine ligands. The corresponding palladium complexes have also been effectively demonstrated to be active catalysts in Suzuki−Miyaura C−C cross-coupling reactions, particularly for sterically demanding substrates. The solution NMR and structural analysis revealed an unexpected intramolecular π−π interaction between the CDC and phosphine ligands within the palladium complexes, which served as an invisible bridging linkage to enforce a cis conformation of the complex. The computational studies supported that the π−π I


Article

Organometallics

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interaction has a positive influence on the activity of the catalytic reaction, which is unprecedented. This work represents a proof of concept for carbodicarbene−phosphinepromoted metal catalysis via an intramolecular π−π interaction. The implications for catalysis and the extension to a wide variety of ligands containing π systems are underway in our laboratories, and these results will open new directions for the catalysis community.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00692. Cartesian coordinates of the calculated structures (XYZ) Experimental details and characterization data of 1, 2PPh3, 2-PTol3, and 2-PCy3, including their catalytic reactions in C−C cross-coupling reactions, and computational details and energies of the calculated structures (PDF) Accession Codes

CCDC 1573441−1573443 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail for L.Z.: [email protected]. *E-mail for T.-G.O.: [email protected]. ORCID

Tiow-Gan Ong: 0000-0001-9817-6300 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by the Ministry of Science & Technology of Taiwan (MOST-104-2628-M-001-005-MY4 grant) and an Academia Sinica Career Development Award (104-CDA-M08). The theoretical work was supported by Nanjing Tech University (Grant No. 39837123), and a SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials, Natural Science Foundation of Jiangsu Province for Youth (Grant No. BK20170964), and National Natural Science Foundation of China (Grant No. 21703099).

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REFERENCES

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Article

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Invisible Chelating Effect Exhibited between Carbodicarbene and

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