Skip to main content
NCBI home page
ACS AuthorChoice logoLink to ACS AuthorChoice
. 2023 Mar 7;13(6):3934–3948. doi: 10.1021/acscatal.3c00075

Important Role of NH-Carbazole in Aryl Amination Reactions Catalyzed by 2-Aminobiphenyl Palladacycles

Raquel J Rama †,‡, Celia Maya §, Francisco Molina ∥, Ainara Nova ‡,*, M Carmen Nicasio †,*
PMCID: PMC10029719  PMID: 36970467

Abstract

graphic file with name cs3c00075_0026.jpg

2-Aminobiphenyl palladacycles are among the most successful precatalysts for Pd-catalyzed cross-coupling reactions, including aryl amination. However, the role of NH-carbazole, a byproduct of precatalyst activation, remains poorly understood. Herein, the mechanism of the aryl amination reactions catalyzed by a cationic 2-aminobiphenyl palladacycle supported by a terphenyl phosphine ligand, PCyp2ArXyl2 (Cyp = cyclopentyl; ArXyl2 = 2,6-bis(2,6-dimethylphenyl)phenyl), P1, has been thoroughly investigated. Combining computational and experimental studies, we found that the Pd(II) oxidative addition intermediate reacts with NH-carbazole in the presence of the base (NaOtBu) to yield a stable aryl carbazolyl Pd(II) complex. This species functions as the catalyst resting state, providing the amount of monoligated LPd(0) species required for catalysis and minimizing Pd decomposition. In the case of a reaction with aniline, an equilibrium between the carbazolyl complex and the on-cycle anilido analogue is established, which allows for a fast reaction at room temperature. In contrast, heating is required in a reaction with alkylamines, whose deprotonation involves coordination to the Pd center. A microkinetic model was built combining computational and experimental data to validate the mechanistic proposals. In conclusion, our study shows that despite the rate reduction observed in some reactions by the formation of the aryl carbazolyl Pd(II) complex, this species reduces catalyst decomposition and could be considered an alternative precatalyst in cross-coupling reactions.

Keywords: amination, palladacycle, phosphine, DFT calculations, microkinetic modeling, reaction mechanism

Introduction

The Pd-catalyzed aryl amination, known as the Buchwald–Hartwig reaction,1,2 is the most direct route for the synthesis of aromatic amines,3−5 useful intermediates for the chemical and pharmaceutical industry.6−9 Over the past 2 decades, a valuable collection of Pd-based catalyst systems has emerged that are very active for the coupling of (hetero)aryl chlorides with a wide range of challenging N-nucleophiles (i.e., primary alkylamines, amides, N-heterocycles, and ammonia).10−17 Its common feature is that they are supported by sterically demanding and electron-rich ancillary phosphines and, to a lesser extent, N-heterocyclic carbene18−20 (NHCs) ligands. Prime examples of phosphine ligands used include bis-phosphines such as Josiphos21,22 and monophosphines like biaryl phosphines,23−25 CataCXium P,26,27 or Mor-DalPhos.28 In parallel with the ligand design, experimental29−33 and computational33−39 studies have been performed to understand the influence of the ligand, reactants, the base, and the solvent in the productive part of the catalytic cycle, namely, the oxidative addition, the ligand exchange, and the reductive elimination steps (Scheme 1). Furthermore, the key role of monoligated LPd(0)40−42 as the catalyst active species34,35 has also been rationalized.

Scheme 1. General Catalytic Cycle for the Buchwald–Hartwig Amination.

Scheme 1

Open in a new tab

On the contrary, off-cycle reactions such as catalyst activation are often ignored.43 The activation step usually involves the formal reduction of the stable Pd(II) precursor into the active monoligated LPd(0) species, affecting the overall rate and selectivity of the cross-coupling reaction.44 The analysis of the reduction to Pd(0) becomes more complex when the catalyst is produced in situ by mixing a Pd(II) salt with a large excess ligand.45 In recent years, the use of well-defined Pd(II) precatalysts with an optimal L/Pd ratio of 1:1 has led to considerable improvement in the effectiveness and applicability of cross-coupling reactions.46,47 This approach is more cost-effective than in situ protocols when sophisticated ligands are employed. However, the use of Pd(II) complexes as precatalysts introduces new players in the catalytic scenario, the spectator ligands. Such ligands are actively involved in the activation step, but they can also participate in additional off-cycle reactions, resulting in a decrease in catalytic activity. Evidence of this is the catalyst deactivation pathway found for [Pd(L)Cl(allyl)] (L = NHC, phosphine) precatalysts by formation of a Pd(I) dimer stabilized by a bridging allyl ligand.48−51

Palladacycles derived from 2-aminobiphenyl, supported by biaryl phosphines, are another family of Pd precatalysts widely used in cross-coupling reactions52−54 due to their easy activation under basic conditions.53 During their activation, NH-carbazole, arising from the 2-aminobiphenyl scaffold (vide infra), is released as a byproduct in the reaction media. An inhibiting effect of NH-carbazole has been documented in some cross-coupling reactions catalyzed by 2-aminobiphenyl-based palladacycles.55−58 Moreover, Colacot and co-workers have postulated, based on kinetic experiments, that the formation of a stable [Pd(L)(Ar)(carbazolyl)] complex resulting from the reaction of NH-carbazole and the Pd(II)-oxidative addition intermediate, which was characterized by X-ray diffraction, is responsible for the reduction in the catalytic activity.57 However, no computational studies of the complete catalytic cycle, including precatalyst activation, have been undertaken.

Recently, we examined the behavior of a family of dialkylterphenyl phosphines59−61 in Pd-catalyzed aryl amination reactions using 2-aminobiphenyl-derived palladacycles as precatalysts.62,63 We found that the cationic palladacycle with the sterically demanding phosphine PCyp2ArXyl2, P1 (Scheme 1), displayed excellent performance and provided a broader substrate scope in the amination of deactivated aryl chlorides with N-nucleophiles, including primary and secondary alkyl and arylamines and N-heterocycles such as indoles (Table 1). To understand the reasons for the high activity and broad applicability of palladacycle P1, we decided to investigate the mechanism of aryl amination reactions catalyzed by P1, including the precatalyst activation step, by experiments and calculations. In this paper, we discuss the role of [Pd(L)(Ph)(carbazolyl)] species as the catalyst resting state, modulating the concentration of the Pd(0) active species, which enters the catalytic cycle. Furthermore, the comparative study using two different N-nucleophiles, anilines, and primary alkylamines helped identify two distinct pathways for the ligand exchange step. Finally, the proposed mechanism is validated and further analyzed using microkinetic modeling.

Table 1. N-Arylation of Various N-Nucleophiles with the Precatalyst P1a.

graphic file with name cs3c00075_0022.jpg

graphic file with name cs3c00075_0023.jpg

Open in a new tab
a

Reaction conditions: aryl chloride (1 mmol), amine (1.2 mmol), [Pd] (0.5 mol %), NaOtBu (1.2 mmol), THF (1 mL), 19 h (unoptimized). Yields of isolated products.

b

Aryl chloride (0.5 mmol), indole (0.53 mmol), [Pd] (1 mol %), 18 h (unoptimized).

Results and Discussion

The computational study was performed on the reaction of chlorobenzene with two amines, aniline and methylamine, as simplified models for the substrates presented in Table 1. For this study, we used density functional (DFT) methods (M06/def2SVP/SMD//M06/def2TZVP/SMD). The influence of the electronic properties of the substrates was also evaluated in both the oxidative addition and the reductive elimination steps. The base NaOtBu was modeled in its tetrameric form considering the nonpolar solvent environment. Results using this model were found to be more consistent with experimental data than using the tBuO– anion (see the Supporting Information for details).

Precatalyst Activation Step

It has been proposed55,64,65 that the reduction of 2-aminobiphenyl palladacycles to the monoligated LPd(0) species takes place by the deprotonation of the amino group in the presence of the base, followed by reductive elimination of NH-carbazole (Scheme 2).

Scheme 2. Activation of 2-Aminobiphenyl Palladacycles.

Scheme 2

Open in a new tab

An intramolecular pathway starting by the coordination of the base to the metal center followed by the deprotonation of the coordinated amino group in palladacycle P1 is shown in Figure 1. In this pathway, the alkoxide group plays a dual role as a ligand and a base. This process involved the binding of tBuO– to the Pd(II) center through rotation of the terphenyl ring of the phosphine to form intermediate P2. The deprotonation and subsequent dissociation of tert-butanol produced intermediate P4, which underwent reductive elimination to give the (PCyp2ArXyl2)Pd(0) active species, 1, and NH-carbazole as a byproduct. The overall process was highly exergonic, and both the deprotonation and the reductive elimination steps had activation barriers of only 10.1 and 11.3 kcal mol–1, respectively. An intermolecular pathway mediated by an external base was also considered unsuccessfully.66

Figure 1.

Figure 1

Open in a new tab

Gibbs energy profile for the precatalyst activation step. Energies in kcal mol–1.

Calculated energy barriers suggest that the activation of P1 is fast under the catalytic conditions (T > 80 °C) and that they should be overcome at ambient temperature.67 To demonstrate the feasibility of P1 activation at milder conditions, we carried out the reaction of P1 with an excess of the base NaOtBu (2 equiv) in toluene-d8 at room temperature (Scheme 3A). After 1.5 h, we observed the development of a black precipitate as a result of the decomposition of the purported monoligated LPd(0) species into metallic palladium. 1H NMR analysis of the reaction crude confirmed the formation of carbazole and tBuOH in ca. 1:1 ratio (see the Supporting Information, Figure S14).

Scheme 3. Reaction of P1 with NaOtBu under Various Conditions.

Scheme 3

Open in a new tab

To trap the monoligated (PCyp2ArXyl2)Pd(0) species, we performed the reaction of the palladacycle with the base in the presence of dibenzylideneacetone, dba (5-fold excess), at room temperature (Scheme 3B). The olefin adduct, 1-dba, was obtained as dark-orange crystals by storing a saturated diethyl ether solution at low temperature. However, its purification proved difficult as it was not possible to remove dba from the product even after several recrystallizations. To circumvent this problem, the complex 1-dba was directly prepared from the reaction of Pd(CH2SiMe3)2(cod) with equimolar amounts of dba and phosphine in diethyl ether at room temperature (see the Supporting Information for details).

The zero-valent complex 1-dba is remarkably stable in solution and can be kept intact for longer periods under a nitrogen atmosphere. 1H and 31P NMR spectra of 1-dba exhibited very broad signals at room temperature, which, upon cooling at −40 °C, resolved into two singlets at 55.6 and 54.0 ppm in the 31P NMR, in an approximate ratio of 1:8 (Figure S15). Since dba can adopt diverse conformations, different isomers are frequently observed for dba adducts in solution.29−31,68−70 The molecular structure of 1-dba was elucidated by single-crystal X-ray diffraction (Figure 2). The Pd center is bonded to one of the alkene groups of the dba and exhibits a nonsymmetric η2–Cipso,–Cortho interaction with a closer flanking aryl ring of the phosphine. The shorter Pd–Cipso (C15) distance of 2.329(8) Å compares well to those found in analogous Pd(0) dba adducts supported by biaryl phosphine ligands (2.298–2.374 Å).71−73 However, the Pd lies at a longer distance from the Cortho (C21) atom (2.533(8) Å). The bond distances Pd–P (2.313(2) Å) and Pd–Colefin (2.114(7) and 2.162(8) Å) are in the range found in the literature for similar complexes.16,71−78

Figure 2.

Figure 2

Open in a new tab

Molecular structure of 1-dba. Hydrogen atoms are omitted for clarity and thermal ellipsoids are set at the 50% level probability. Selected distances [Å] and angles [°]: Pd–P 2.313(2), Pd–C39 2.162(8), Pd–C40 2.114(7), Pd–C15 2.329(8), Pd–C21 2.533(8), C39–C40 1.423(11), C48–C49 1.325(12).

Oxidative Addition

It has been established that prior to oxidative addition, chlorobenzene interacts with monoligated Pd(0) species 1 through the aromatic ring forming an arene complex 2(34,35,79) (Figure 3). We found that the lowest energy isomer (−11.0 kcal mol–1) shows η2-coordination with Cortho and Cmeta atoms of the PhCl ring (Figure S7). Intermediate 2 underwent oxidative addition rendering complex 3. This step was a downhill process with a calculated barrier of 12.6 kcal mol–1 relative to 2, in line with those reported for the reaction of chlorobenzene with a monoligated Pd(0) complex.37,78,80 The oxidative addition product 3 showed a trans orientation of the chloride and phosphine ligands. The low activation barrier found for the formation of 3 suggests that the oxidative addition of PhCl to 1 can also proceed at ambient temperature.

Figure 3.

Figure 3

Open in a new tab

Gibbs energy profile for the oxidative addition step. Energies are in kcal mol–1.

We found it interesting to evaluate the electronic effect of ArCl bearing electron-donating and -withdrawing groups at the p-position of the aryl ring in the oxidative addition step. For all of them, a conformational study of the possible isomers for intermediate 2 was also performed (Figures S7 and S8). As expected, the highest activation barrier for the 2 → 3 step was obtained for electron-rich 4-chloroanisole (16.0 kcal mol–1) and the lowest for electron-deficient 4-chlorobenzaldehyde (11.1 kcal mol–1).81 These energy barriers suggest that the oxidative addition should be feasible at room temperature, even for the less reactive substrates.

We isolated and structurally characterized a variety of oxidative addition complexes 3 following the procedure depicted in Scheme 4.82,83 These complexes were obtained as air-stable solids in moderate to good yields.84

Scheme 4. Synthesis of Oxidative Addition Products 3.

Scheme 4

Open in a new tab

The 31P{1H} spectra of complexes 3 consisted of a single resonance at ca. 46 ppm (Δδ of ca. 40 ppm at a higher frequency with respect to the free ligand). This difference in 31P chemical shift,60 together with the observation of slow rotation of the phosphine ligand around the P–Cipso bond in their 1H NMR spectra, pointed toward a bidentate coordination mode of the terphenyl phosphine (k2-P, η1-Cipso). Structures of complexes 3 were established by X-ray diffraction studies carried out with 3OMe(84) and 3CN (Figure 4).

Figure 4.

Figure 4

Open in a new tab

Molecular structures of oxidative addition complexes 3OMe and 3CN. Hydrogen atoms are omitted for clarity, and thermal ellipsoids are set at the 50% level probability. Selected distances [Å] and angles [°] for 3CN: Pd–P 2.2617(7), Pd–Cl 2.3471(7), Pd–C7 2.457(2), Pd–C33 1.992(3), P–C1 1.851(2); Cl–P–dC33 83.68(7), P–Pd–C7 83.06(7), P–Pd–Cl 169.32(3), C7–Pd–C33 162.17(10).

Complexes 3 are mononuclear in the solid state. Both P and Cl atoms display a trans-arrangement, and the Pd(II) center features an η1 interaction with the ipso–carbon bond of the nearby side aryl ring of the phosphine. The Pd–Cipso contacts are rather long (2.426(2) Å for 3OMe and 2.457(2) Å for 3CN) but fit within the range 2.22–2.45 Å found for the η1 coordinate arene to a d8-ML3 fragment and compare well to those reported for biaryl phosphine analogues.83 The length of the Pd–aryl bond in both complexes is nearly identical (2.000(2) and 1.992(3) Å for 3OMe and 3CN, respectively) despite the significant difference in the electron-donating ability of the aryl ring.

According to the calculations, the formation of intermediate 3 should take place rapidly at room temperature. To corroborate the computational finding, we studied the reaction of palladacycle P1 with chlorobenzene in the presence of an excess of the base, NaOtBu, at room temperature (Figure S18). To our surprise, the reaction did not produce the expected oxidative addition product but a Pd(II) complex containing a carbazolyl ligand, 8OMeCz (Scheme 5a). As suggested by Colacot, this compound may result from the reaction of the oxidative addition product 3 with a carbazolyl anion, coming from the deprotonation of the NH-carbazole byproduct (released during P1 activation) in the presence of the base. To validate this hypothesis, we performed the synthesis of 8Cz and 8OMeCz by reacting 3 and 3OMe with carbazole under basic conditions (Scheme 5b).

Scheme 5. Synthesis of Carbazole-Containing Products 8Cz and 8OMeCz.

Scheme 5

Open in a new tab

The complexes 8Cz and 8OMeCz were isolated in high yields as air-stable orange crystalline solids. They were fully characterized by elemental analysis and NMR spectroscopy, and the structure of 8OMeCz was confirmed by X-ray crystallography. As shown in Figure 5, the carbazolyl ligand occupies the trans-position to the phosphine in the square planar coordination geometry. The Pd–Cipso distance (2.456(3) Å) is similar to that found in oxidative addition products 3OMe and 3CN. Furthermore, the Pd–N distance of 2.054(2) Å is similar to those of other tricoordinate monoligated Pd–amido complexes.86

Figure 5.

Figure 5

Open in a new tab

Molecular structure of 8OMeCz. Hydrogen atoms are omitted for clarity and thermal ellipsoids are set at the 50% level probability. Selected distances [Å] and angles [°]: Pd–P 2.2755(7), Pd–N 2.054(2), Pd–C7 2.456(3), Pd–C46 2.004(3), P–C1 1.853(3); N–Pd–C46 83.62(10), P–Pd–C7 82.92(6), C7–Pd–C33 162.17(10).

X-ray structures of carbazolyl-containing complexes of late transition metals are scarce. We are aware of only one example of a Pd(II)–carbazolyl complex supported by the biaryl phosphine RuPhos described by Colacot and co-workers,57 whose structure is closely related to that of 8OMeCz. The role of the carbazolyl complex 8Cz in the catalytic cycle will be discussed in detail below.

To avoid the formation of the carbazolyl complex 8Cz, palladacycle P1′, bearing the N-methyl-2-aminobiphenyl ligand, was employed in the reaction with chlorobenzene and the base (Scheme 6). The activation of P1′ would render the formation of monoligated species 1 and N-methyl-carbazole as a byproduct, which could not be further deprotonated. NMR monitoring the reaction in C6D6 confirmed the formation of the expected oxidative addition product 3 along with the N-methylcarbazole byproduct (Figure S16).

Scheme 6. Formation of the Oxidative Addition Product 3 from P1′.

Scheme 6

Open in a new tab

Ligand Exchange

After the oxidative addition, the amine and the base (tBuO–) may compete for coordinating the metal center in 3. We analyzed three different pathways for chloride replacement and amine deprotonation (see the Supporting Information for details). For aniline, we found that the most favorable route involved the substitution of the chloride ligand in 3 by tBuO– leading to the intermediate 3-OtBu (Figure 6). Dissociation of the Pd–Cipso interaction and aniline coordination produced the intermediate 5A (A for aniline), which, after intramolecular deprotonation, dissociation of tBuOH, and restoration of the Pd–Cipso interaction, resulted in the formation of the amido complex 8A, located at −27.4 kcal mol–1. The overall barrier for this pathway was 6.4 kcal mol–1, consistent with a rapid process. It should be noted that the alkoxide anion was acting both as a nucleophile87 and as a base, in contrast to the common role as a deprotonation agent found for tBuO– in reported computational studies.34−39 To confirm the computational prediction of a facile substitution of the chloride by the base in 3, the reaction of complex 3 with NaOtBu (10 equiv) at room temperature was monitored by 31P NMR spectroscopy. After 30 min of reaction, we observed a mixture of two species in ca. 1:3.7 ratio (Figure S17). The minor component corresponded to unreacted 3 and the major one to a new complex, which originated a signal at 37.6 ppm that was tentatively assigned to the alkoxide adduct. However, repeated attempts at isolating such species proved fruitless.

Figure 6.

Figure 6

Open in a new tab

Gibbs energy profile for the reaction of 3 with aniline and the base. Gibbs energies are in kcal mol–1.

As aniline is a weak base (pKa = 30.6 in DMSO) and a weak nucleophile, we also considered the possibility of the nonmetal-assisted deprotonation of aniline by the alkoxide base.37 Despite the higher energy of formation of the anilide anion (13.1 kcal mol–1, Figure 6), the nonmetal-assisted pathway should be accessible at room temperature.

A different scenario was found for a primary alkylamine. Using methylamine as the model substrate, the more feasible route agreed with those calculated previously34−39 and involves the direct coordination of the amine to an empty site trans to the P atom to give the intermediate 5M (M for methylamine),78,88,89 which is 1.1 kcal mol–1 lower in energy than 3 (Figure 7 and Scheme S1). From 5M, intermolecular deprotonation and chloride extraction take place, leading to the intermediate 8M at −18.6 kcal mol–1. The transition state for the proton transfer could not be located, but this value was fitted to reproduce the experimental results using the microkinetic model (vide infra). Unlike aniline, the coordination/deprotonation of methylamine is an endergonic process.

Figure 7.

Figure 7

Open in a new tab

Gibbs energy profile for the reaction of complex 3 with methylamine and the base. Gibbs energies are in kcal mol–1. aStructure optimized with a fixed Ph–Pd–Cl angle to estimate the TS energy between 3 and 5M. *This value has been fitted using the microkinetic model.

To support these results, we tested the reactivity of complex 3 with a large excess of hexylamine or morpholine in toluene, at room temperature (Scheme 7). Complexes 5M were fully characterized by analytical and spectroscopic methods. In solution, both complexes dissociated the amine ligand, leading to mixtures of amino adducts and the oxidative addition product 3. Efforts to grow crystals of any of the amino adducts suitable for X-ray diffraction studies proved unsuccessful. Conversely, no reaction was observed when 3 was treated with an excess of aniline, confirming the differences in the ligand exchange step for the two types of amines.

Scheme 7. Synthesis of Amine Adducts.

Scheme 7

Open in a new tab

Reductive Elimination

In the last step of the catalytic cycle, the reductive elimination from the anilido complex 8A proceeds with a barrier of only 13.6 kcal mol–1 to form the amine Pd(0) complex 9A (−44.7 kcal mol–1). Substitution of diphenylamine by the chlorobenzene initiates a new catalytic cycle (Figure 8).

Figure 8.

Figure 8

Open in a new tab

Gibbs energy profile for the reductive elimination step. Gibbs energies are in kcal mol–1.

The influence of the electronic properties of both the aryl and amido groups on the reductive elimination step was taken into consideration. We calculated the reductive elimination barriers of anilido complexes bearing p-substituted aryl groups with different electronic properties (Table 2 and Figure S12). In agreement with previous experimental data,90,91 electron-rich aryl groups hampered the C–N reductive elimination, whereas electron-deficient aryl rings facilitated the process. The difference in the activation barrier between the least (4-MeO–C6H4) and most reactive (4-OHC–C6H4) anilido complexes was found to be 4.8 kcal mol–1. Moreover, barriers found for the C–N reductive elimination of amido ligands derived from primary alkylamine (methylamine), secondary amines (dimethyl amine and N-methylaniline), and N-heterocycle (carbazole) showed that the more electron-rich the amido group, the faster the reaction90,91 (Table 2 and Figure S13).

Table 2. Energies of Aryl Amido Complexes [(PCyp2ArXyl2)Pd(Ar)(amido)] and Reductive Elimination Transition States in kcal mol–1.

aryl group aryl anilido complex transition state ΔG‡
4-OHC-C6H4 –29.8 –20.3 9.5
4-CF3-C6H4 –28.3 –16.9 11.4
C6H5 –27.4 –13.8 13.6
4-OMe-C6H4 –26.7 –12.4 14.3
amido group phenyl amido complex transition state ΔG‡
MeNH2 –18.6 –10.5 8.1
Me2NH –20.5 –10.8 9.7
PhNH –27.4 –13.8 13.6
PhMeN –29.2 –13.5 15.7
carbazolyl –39.3 –16.9 22.4
Open in a new tab

Interestingly, not only is the carbazolyl complex the most stable amido intermediate, but it is also 17.0 kcal mol–1 lower in energy than the oxidative addition product 3. Such pronounced stability along with the substantial barrier of 22.4 kcal mol–1 for the reductive elimination facilitated the isolation of the carbazolyl intermediate 8Cz from reactions outlined in Scheme 5. Efforts to prepare other alkyl or aryl amido complexes resulted in the formation of the C–N coupling product, supporting a facile reductive elimination step in these cases.

Role of the Pd–Carbazolyl Complex

As described above, Colacot and co-workers detected the formation of a Pd–carbazolyl complex in aryl amination reactions catalyzed by a RuPhos-supported palladacycle and studied the reductive elimination of N-phenylcarbazole from Pd(C6H5)(carbazolyl)(RuPhos), independently prepared.55−58

The formation of the compound 8Cz from 3, carbazole, and NaOtBu was studied by DFT calculations (Figure 9). Carbazole is deprotonated by the base forming species BaseCz, which is energetically favored by 4.0 kcal mol–1. This result is consistent with the acidic character of carbazole (pKa = 19.9 in DMSO).92 The replacement of the chloride by the carbazolyl anion in 3 produces the intermediate 8Cz, located at −39.3 kcal mol–1. The transition state of the chloride replacement has been set using the microkinetic model (vide infra).

Figure 9.

Figure 9

Open in a new tab

Gibbs energy profile for the formation of the 8Cz complex. Gibbs energies are in kcal mol–1. *This value has been fitted using the microkinetic model.

To shed light on the role of the aryl carbazolyl complex [(PCyp2ArXyl2)Pd(Ar)(carbazolyl)], 8Cz, under catalytic conditions, a set of experiments was carried out. First, we studied the reductive elimination of N-arylcarbazole from the complex 8OMeCz. As summarized in Scheme 8A, the compound 8OMeCz underwent reductive elimination upon heating in C6D6 at 80 °C in 2 h, affording the corresponding C–N coupling product, free phosphine (observed by 31P NMR spectroscopy), and a black precipitate of Pd(0) (Figure S20). When accomplishing the reaction in the presence of 1.5 equiv of dba, the (PCyp2ArXyl2)Pd(0) species could be efficiently trapped as the dba adduct, 1-dba (Figure S21). We found that the complex 8OMeCz experienced a faster reductive elimination compared to that of the analogous RuPhos complex, for which a half-life time of 91 min has been reported.53 Presumably, the bulkiness of the terphenyl phosphine ligand may account for such a difference.

Scheme 8. (A) Thermal Reductive Elimination of N-Arylcarbazole from 8OMeCz, (B) Cross-Coupling of 4-Chloroanisole with Aniline Using P1, and (C) Cross-Coupling of Chlorobenzene and n-Hexylamine Using P1.

Scheme 8

Open in a new tab

Next, we monitored by 31P NMR spectroscopy the coupling between 4-chloroanisole and aniline in C6D6 at ambient temperature using 2.0 mol % of the precatalyst P1 (Scheme 8B). Within 15 min of reaction, we observed a species whose 31P chemical shift (ca. 42 ppm) matched that of the Pd–carbazolyl complex, in addition to the free ligand and phosphine oxide (see Figure S22 for NMR details). The concentration of this species decreased as the reaction proceeded. A similar experiment carried out with n-hexylamine and chlorobenzene, at room temperature, revealed the presence of the Pd–carbazolyl complex as the major phosphorus-containing species after 20 min of reaction, which disappeared when the reaction reached completion after 5 days (Scheme 8C and Figure S23).

Collectively, these experiments suggest that the complex [(PCyp2ArXyl2)Pd(Ar)(carbazolyl)], 8Cz, is the catalyst resting state. In support of this, using 8Cz as the precatalyst for the coupling of chlorobenzene with either aniline or n-hexylamine gave the same outcome as the precatalyst P1 under the same conditions (see Table 3 below).

Table 3. Catalytic Performance of Isolated Intermediates in the C–N Coupling of Chlorobenzene with Amines at Room Temperaturea.

graphic file with name cs3c00075_0024.jpg

graphic file with name cs3c00075_0025.jpg

Open in a new tab
a

Reaction conditions: chlorobenzene (1 mmol), amine (1.2 mmol), [Pd] (0.5 mol%), NaOtBu (1.2 mmol), THF (1 mL), 24 h (unoptimized); yields of isolated products (average of two runs). GC conversion in parenthesis.

b

4-chloroanisole (1 mmol) as aryl chloride.

c

T = 80 °C.

d

T = 110 °C.

e

Reaction time: 4 h.

We also investigated the behavior of the carbazolyl complex 8Cz toward the amine in the presence of the base at room temperature. Gas chromatography (GC) analysis of the reaction with aniline confirmed the presence of N-phenylcarbazole and diphenylamine. Conversely, when the experiment was carried out with n-hexylamine, only N-phenylcarbazole was detected by GC. These findings suggest that the carbazolyl ligand in 8Cz could exchange with the anilide anion, establishing an equilibrium between 8Cz and the anilide complex 8A, favoring the former. Since n-hexylamine could not be deprotonated without the assistance of the Pd center, a similar equilibrium cannot be established.

Mechanistic Proposal and Microkinetic Modeling

On the basis of computational and experimental data, the proposed mechanisms for the amination of the aryl chloride reaction catalyzed by palladacycle P1 are shown in Figure 10.

Figure 10.

Figure 10

Open in a new tab

Proposed catalytic cycle for aniline (blue pathway) and methylamine (green pathway).

For aromatic and aliphatic amines, precatalyst activation, oxidative addition, and reductive elimination are common steps. The activation of the palladacycle in the presence of the base is a highly exergonic and low-barrier step (ΔGAct = −31.4 and ΔGRE‡ = 11.3 kcal mol–1). The activation generates a noninnocent byproduct, NH-carbazole, that, after deprotonation, coordinates to the oxidative addition product 3 producing a very stable aryl carbazolyl complex 8Cz. The barrier for the reductive elimination of N-arylcarbazole (22.4 kcal mol–1) is the highest of all of the barriers computed for the different steps of the catalytic cycle. This species serves as the catalyst resting state, as inferred from NMR experiments as well as microkinetic analysis (vide infra). The existence of an equilibrium between the carbazolyl complex 8Cz and the anilido analogue 8A provides a faster route for the C–N coupling even at room temperature since the reductive elimination barrier from the latter is much smaller. However, such an equilibrium is not feasible for a more basic amine, such as methylamine (pKaca. 42 in DMSO), which requires temperatures higher than the ambient temperature to facilitate the reductive elimination of N-arylcarbazole and the release of the catalytically active species.

Oxidative addition (ΔG‡ = 12.6 kcal mol–1) and reductive elimination (ΔG‡ = 13.6 kcal mol–1 for aniline and 8.1 kcal mol–1 for methylamine) steps have low energy barriers comparable to those found for the Pd catalyst systems bearing bulky, electron-rich ligands.34−39 For the ligand exchange step, two different pathways are found, which depend on the nucleophilicity and basicity of the amine employed. Due to the less nucleophilic character of aniline, the oxidative addition complex 3 reacts first with the base (tBuO–), leading to a neutral alkoxide intermediate 3-OtBu, from which the aryl amido intermediate 8A is easily obtained. Concurrently, aniline could also be deprotonated without the assistance of the metal center, providing a more direct route to the intermediate 8A. When a more nucleophilic amine is employed (e.g., primary alkylamine), amine coordination to oxidative addition complex 3 and intermolecular deprotonation by the base comprise the lower energy pathway to give 8M.

Given that energy barriers found for most steps of the catalytic cycles could be surmounted at room temperature, we examined the C–N coupling of chlorobenzene with aniline and with n-hexylamine using the precatalyst P1 at room temperature. While aniline provided quantitative yields of the diphenylamine product, n-hexylamine gave around 50% of the corresponding C–N coupling product (Table 3, entries 1 and 6). Moreover, identical results were obtained when the carbazolyl complex 8Cz was used as the precatalyst (Table 3, entries 2 and 7). However, for the reaction with n-hexylamine, a notable improvement in yield was observed when on-cycle intermediates (oxidative addition product 3 and amino adduct 5M-Hex) were tested as precatalysts (Table 3, entries 8 and 9). We also analyzed the room-temperature C–N couplings in the presence of palladacycle P1′, which generated N-methylcarbazole upon activation. The reaction with aniline produced identical results to that with palladacycle P1 (entry 5), but with the alkylamine, the conversion and yield were akin to those obtained with on-cycle intermediates (entry 10). These results show that the carbazolyl species 8Cz reduces the rate of the coupling reactions with alkylamines at room temperature, but it does not affect the rate of the coupling with aniline (Figure S24). Despite this, when testing the catalytic performance of precatalysts P1, P1′, and 3 in the thermal reaction between 4-chloroanisole and morpholine, palladacycle P1 performed significantly better than P1′ and outperformed 3 under the same reaction conditions (Table 3, entries 11–14). These findings suggest that the carbazolyl species 8Cz could prevent fast deactivation of the catalytically active species, maintaining most palladium species within the productive part of the catalytic cycle.

To assess our mechanistic proposal and estimate missing energy barriers involving the base, we built a microkinetic model (see the Supporting Information for details). This technique allows one to simulate the evolution of the concentration of each species with time using rate constants provided by DFT calculations and initial concentrations provided by experiments.93,94 Microkinetic modeling offers a more realistic description of the catalytic system, and although it is widely used in heterogeneous catalysis, it has been scarcely applied to organometallic catalysis.95−97

For the C–N coupling between chlorobenzene and aniline catalyzed by palladacycle P1, the model predicted a fast reaction at room temperature. As shown in Figure 11A, the microkinetic model reproduces satisfactorily the experimental results. The noncomputed barriers were adjusted to fit the shape of the experimental trend (see the Supporting Information for details).

Figure 11.

Figure 11

Open in a new tab

Comparison of experimental and modeled kinetic data for the C–N coupling of chlorobenzene with (A) aniline and (B) primary alkylamine (hexylamine for the experiments and methylamine for the calculations) at room temperature.

However, when the microkinetic analysis was applied to the C–N coupling between chlorobenzene and methylamine, full conversion to N-methylaniline was reached in only 7 min at room temperature. This result clearly contrasts with the slow reaction observed at room temperature (Table 3, entry 6). To reproduce the experimental data, we evaluated the energy barriers for each of the individual steps of the catalytic cycle using the experimental information from the isolated reactions (see the Supporting Information). We found that the computed barrier for the reductive elimination of N-arylcarbazole from the intermediate 8Cz (22.4 kcal mol–1) was underestimated by 2.0 kcal mol–1. Moreover, the barrier associated with the transition state for the deprotonation of the coordinated methylamine 5M-Base, which could not be located, has to be adjusted to 21.0 kcal mol–1 (see Figure 7). With these optimized values, a good agreement between the model output and experimental kinetic data was obtained (Figure 11B). It is important to note that these fittings do not affect the results of the reaction with aniline. In addition, the microkinetic model predicted full conversions for the arylation of methylamine using complexes 3 and the amine adduct 5M-Hex as precatalysts, in excellent agreement with those obtained in experiments depicted in Table 3 (entries 8 and 9).

The microkinetic analysis also showed that the carbazolyl complex 8Cz was the catalyst resting state. Its concentration remains constant during the progress of the reaction with aniline. However, in the reaction with an alkylamine, 5M-base is formed in the first stage of the reaction at a high concentration of amine. When 18% of the amine has reacted, the complex 8Cz is the major Pd-containing species, and its concentration decreases during the course of the reaction due to the reductive elimination of N-phenylcarbazole. In contrast, complexes 3 and 5M-base are the resting states of the catalyst in the absence of carbazole, indicating that the reaction with the amine or base is the rate-limiting step.

In short, the results provided by the microkinetic model validate the proposed reaction mechanism. Next, we tested the model to reproduce the selectivity observed in competition experiments between aniline and n-hexylamine. These experiments were conducted using 3-chloroanisole as the electrophilic coupling partner. Under the standard reaction conditions, there was a clear preference for the N-arylation of the primary alkylamine over the aromatic amine (Scheme 9).

Scheme 9. Amine Competition Experiments Using the Precatalyst P1.

Scheme 9

Open in a new tab

Reaction conditions: 3-chloroanisole (0.5 mmol), N-nucleophile (0.6 mmol), [P1] (0.0025 mmol), NaOtBu (0.6 mmol), THF (1 mL), 19 h. Conversions were determined by GC analysis of the reaction mixture using dodecane as the internal standard.

To evaluate the selectivity, we prepared a model that combines the two types of mechanisms found for aniline and methylamine. With the adjustments made previously, the model provided an excellent agreement (see Scheme 9). The largest ratio of alkylamine is attributed to the fast accumulation of the 5M-base intermediate, which is the major Pd-containing species formed in the first stage of the reaction with alkylamine.

Conclusions

The overall catalytic cycle for the aryl amination reaction catalyzed by 2-aminobiphenyl palladacycle supported by terphenyl phosphine, PCyp2ArXyl2, P1, was analyzed in detail by computational and experimental methods. P1 activation and ArCl oxidative addition, ligand exchange, and reductive elimination steps are all characterized by low activation barriers. However, the NH-carbazole byproduct liberated upon P1 activation greatly influences the catalyst’s performance by forming a stable aryl carbazolyl Pd(II) intermediate. Such an intermediate serves as the catalyst resting state, releasing catalytically active monoligated LPd(0) species into the cycle upon reductive elimination of N-arylcarbazole. With less basic amines like aniline, fast reaction occurs at room temperature. The facile deprotonation of aniline enables an equilibrium between the aryl carbazolyl complex and the on-cycle anilido analogue, thus circumventing the higher activation barrier of N-arylcarbazole reductive elimination. Such an equilibrium is precluded with more basic primary alkylamines, which require heating to achieve an efficient transformation. A microkinetic model built with computed barriers and thermodynamics reproduced experimental data and selectivity, validating the proposed catalytic cycles. Furthermore, experimental data allowed estimating barriers that are difficult to calculate.

The results described in this work suggest that the NH-carbazole byproduct formed in reactions catalyzed by 2-aminobiphenyl palladacycles could decrease the reaction rate of some cross-couplings but stabilize the metal center at high temperatures. Furthermore, the stability and ease of tunability of the aryl carbazolyl Pd(II) intermediate open up its use as a precatalyst for cross-coupling reactions.

Acknowledgments

The authors thank MCIN/AEI/ 10.13039/501100011033 (Grant PID2020-113797R), US/JUNTA/FEDER, UE (Grant US-1262266), and FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento (Grant P20_00624) for the financial support. R.J.R. and A.N. acknowledge the support from the Research Council of Norway through the Centre of Excellence (No. 262695) and A.N. for its FRINATEK program (314321). R.J.R. thanks the Universidad de Sevilla (V and VI Plan Propio de Investigación) for research fellowships. R.J.R. thanks the Norwegian Metacenter for Computational Science (NOTUR) for computational resources (No. nn4654k). Thanks are also due to Nazaret Santamaría for helping with kinetic experiments.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.3c00075.

  • Computational methods and results; experimental procedures; NMR data, and crystallographic details (PDF)

  • 1-dba (CIF)

  • 3CN (CIF)

  • 8OMeCz (CIF)

  • Optimized coordinates for calculated structures (XYZ)

Accession Codes

CCDC 2221856 (1-dba), 2224943 (3CN), and 2224944 (8OMeCz) contain the supporting crystallographic data for this paper. This data can be obtained free of charge viawww.ccdc.cam.ac.uk/data_request/cif.

The authors declare no competing financial interest.

Supplementary Material

cs3c00075_si_001.pdf (3.1MB, pdf)
cs3c00075_si_002.cif (986.5KB, cif)
cs3c00075_si_003.cif (1.6MB, cif)
cs3c00075_si_004.cif (1.5MB, cif)
cs3c00075_si_005.xyz (502.4KB, xyz)

References

  1. Louie J.; Hartwig J. F. Palladium-Catalyzed Synthesis of Arylamines from Aryl Halides. Mechanistic Studies Lead to Coupling in the Absence of Tin Reagents. Tetrahedron Lett. 1995, 36, 3609–3612. 10.1016/0040-4039(95)00605-C. [DOI] [Google Scholar]
  2. Guram A. S.; Rennels R. A.; Buchwald S. L. A Simple Catalytic Method for the Conversion of Aryl Bromides to Arylamines. Angew. Chem., Int. Ed. 1995, 34, 1348–1350. 10.1002/anie.199513481. [DOI] [Google Scholar]
  3. Ruiz-Castillo P.; Buchwald S. L. Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions. Chem. Rev. 2016, 116, 12564–12649. 10.1021/acs.chemrev.6b00512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dorel R.; Grugel C. P.; Haydl A. M. The Buchwald–Hartwig Amination After 25 Years. Angew. Chem., Int. Ed. 2019, 58, 17118–17129. 10.1002/anie.201904795. [DOI] [PubMed] [Google Scholar]
  5. Hartwig J. F.; Shaughnessy K. H.; Shekhar S.; Green R. A. Palladium-Catalyzed Amination of Aryl Halides. Org. React. 2019, 100, 853–958. 10.1002/0471264180.or100.14. [DOI] [Google Scholar]
  6. Schlummer B.; Scholz U. Palladium-Catalyzed C–N Coupling-A C–O Practical Guide from an Industrial Vantage Point. Adv. Synth. Catal. 2004, 346, 1599–1626. 10.1002/adsc.200404216. [DOI] [Google Scholar]
  7. Torborg C.; Beller M. Recent Applications of Palladium-Catalyzed Coupling Reactions in the Pharmaceutical, Agrochemical, and Fine Chemical Industries. Adv. Synth. Catal. 2009, 351, 3027–3043. 10.1002/adsc.200900587. [DOI] [Google Scholar]
  8. Hapke M. Catalytic Arylation Methods. From the Academic Lab to Industrial Processes. By Anthony J. Burke and Carolina Silva Marques. Angew. Chem., Int. Ed. 2015, 54, 14618–14619. 10.1002/anie.201509471. [DOI] [Google Scholar]
  9. Devendar P.; Qu R.-Y.; Kang W.-M.; He B.; Yang G.-F. Palladium-Catalyzed Cross-Coupling Reactions: A Powerful Tool for the Synthesis of Agrochemicals. J. Agric. Food Chem. 2018, 66, 8914–8934. 10.1021/acs.jafc.8b03792. [DOI] [PubMed] [Google Scholar]
  10. Surry D. S.; Buchwald S. L. Selective Palladium-Catalyzed Arylation of Ammonia: Synthesis of Anilines as Well as Symmetrical and Unsymmetrical Di- and Triarylamines. J. Am. Chem. Soc. 2007, 129, 10354–10355. 10.1021/ja074681a. [DOI] [PubMed] [Google Scholar]
  11. Lundgren R. J.; Peters B. D.; Alsabeh P. G.; Stradiotto M. A P,N-Ligand for Palladium-Catalyzed Ammonia Arylation: Coupling of Deactivated Aryl Chlorides, Chemoselective Arylations, and Room Temperature Reactions. Angew. Chem., Int. Ed. 2010, 49, 4071–4074. 10.1002/anie.201000526. [DOI] [PubMed] [Google Scholar]
  12. Vo G. D.; Hartwig J. F. Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides, and Sulfonates: A General Method for the Preparation of Primary Arylamines. J. Am. Chem. Soc. 2009, 131, 11049–11061. 10.1021/ja903049z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ruiz-Castillo P.; Blackmond D. G.; Buchwald S. L. Rational Ligand Design for the Arylation of Hindered Primary Amines Guided by Reaction Progress Kinetic Analysis. J. Am. Chem. Soc. 2015, 137, 3085–3092. 10.1021/ja512903g. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Brusoe A. T.; Hartwig J. F. Palladium-Catalyzed Arylation of Fluoroalkylamines. J. Am. Chem. Soc. 2015, 137, 8460–8468. 10.1021/jacs.5b02512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Olsen E. P. K.; Arrechea P. L.; Buchwald S. L. Mechanistic Insight Leads to a Ligand Which Facilitates the Palladium-Catalyzed Formation of 2-(Hetero)Arylaminooxazoles and 4-(Hetero)Arylaminothiazoles. Angew. Chem., Int. Ed. 2017, 56, 10569–10572. 10.1002/anie.201705525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weber P.; Scherpf T.; Rodstein I.; Lichte D.; Scharf L. T.; Gooßen L. J.; Gessner V. H. A Highly Active Ylide-Functionalized Phosphine for Palladium-Catalyzed Aminations of Aryl Chlorides. Angew. Chem., Int. Ed. 2019, 58, 3203–3207. 10.1002/anie.201810696. [DOI] [PubMed] [Google Scholar]
  17. McCann S. D.; Reichert E. C.; Arrechea P. L.; Buchwald S. L. Development of an Aryl Amination Catalyst with Broad Scope Guided by Consideration of Catalyst Stability. J. Am. Chem. Soc. 2020, 142, 15027–15037. 10.1021/jacs.0c06139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marion N.; Navarro O.; Mei J.; Stevens E. D.; Scott N. M.; Nolan S. P. Modified (NHC)Pd(Allyl)Cl (NHC = N-Heterocyclic Carbene) Complexes for Room-Temperature Suzuki–Miyaura and Buchwald–Hartwig Reactions. J. Am. Chem. Soc. 2006, 128, 4101–4111. 10.1021/ja057704z. [DOI] [PubMed] [Google Scholar]
  19. Organ M. G.; Abdel-Hadi M.; Avola S.; Dubovyk I.; Hadei N.; Kantchev E. A. B.; O’Brien C. J.; Sayah M.; Valente C. Pd-Catalyzed Aryl Amination Mediated by Well Defined, N-Heterocyclic Carbene (NHC)–Pd Precatalysts, PEPPSI. Chem. - Eur. J. 2008, 14, 2443–2452. 10.1002/chem.200701621. [DOI] [PubMed] [Google Scholar]
  20. Valente C.; Çalimsiz S.; Hoi K. H.; Mallik D.; Sayah M.; Organ M. G. The Development of Bulky Palladium NHC Complexes for the Most-Challenging Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2012, 51, 3314–3332. 10.1002/anie.201106131. [DOI] [PubMed] [Google Scholar]
  21. Shen Q.; Shekhar S.; Stambuli J. P.; Hartwig J. F. Highly Reactive, General, and Long-Lived Catalysts for Coupling Heteroaryl and Aryl Chlorides with Primary Nitrogen Nucleophiles. Angew. Chem., Int. Ed. 2005, 44, 1371–1375. 10.1002/anie.200462629. [DOI] [PubMed] [Google Scholar]
  22. Shen Q.; Ogata T.; Hartwig J. F. Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships. J. Am. Chem. Soc. 2008, 130, 6586–6596. 10.1021/ja077074w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Old D. W.; Wolfe J. P.; Buchwald S. L. A Highly Active Catalyst for Palladium-Catalyzed Cross-Coupling Reactions: Room-Temperature Suzuki Couplings and Amination of Unactivated Aryl Chlorides. J. Am. Chem. Soc. 1998, 120, 9722–9723. 10.1021/ja982250+. [DOI] [Google Scholar]
  24. Surry D. S.; Buchwald S. L. Biaryl Phosphane Ligands in Palladium-Catalyzed Amination. Angew. Chem., Int. Ed. 2008, 47, 6338–6361. 10.1002/anie.200800497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maiti D.; Fors B. P.; Henderson J. L.; Nakamura Y.; Buchwald S. L. Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases. Chem. Sci. 2011, 2, 57–68. 10.1039/C0SC00330A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rataboul F.; Zapf A.; Jackstell R.; Harkal S.; Riermeier T.; Monsees A.; Dingerdissen U.; Beller M. New Ligands for a General Palladium-Catalyzed Amination of Aryl and Heteroaryl Chlorides. Chem. - Eur. J. 2004, 10, 2983–2990. 10.1002/chem.200306026. [DOI] [PubMed] [Google Scholar]
  27. Zapf A.; Beller M. The Development of Efficient Catalysts for Palladium-Catalyzed Coupling Reactions of Aryl Halides. Chem. Commun. 2005, 431–440. 10.1039/b410937f. [DOI] [PubMed] [Google Scholar]
  28. Lundgren R. J.; Sappong-Kumankumah A.; Stradiotto M. A Highly Versatile Catalyst System for the Cross-Coupling of Aryl Chlorides and Amines. Chem. - Eur. J. 2010, 16, 1983–1991. 10.1002/chem.200902316. [DOI] [PubMed] [Google Scholar]
  29. Hartwig J. Palladium-Catalyzed Amination of Aryl Halides: Mechanism and Rational Catalyst Design. Synlett 1997, 1997, 329–340. 10.1055/s-1997-789. [DOI] [Google Scholar]
  30. Alcazar-Roman L. M.; Hartwig J. F.; Rheingold A. L.; Liable-Sands L. M.; Guzei I. A. Mechanistic Studies of the Palladium-Catalyzed Amination of Aryl Halides and the Oxidative Addition of Aryl Bromides to Pd(BINAP)2 and Pd(DPPF)2: An Unusual Case of Zero-Order Kinetic Behavior and Product Inhibition. J. Am. Chem. Soc. 2000, 122, 4618–4630. 10.1021/ja9944599. [DOI] [Google Scholar]
  31. Shekhar S.; Ryberg P.; Hartwig J. F.; Mathew J. S.; Blackmond D. G.; Strieter E. R.; Buchwald S. L. Reevaluation of the Mechanism of the Amination of Aryl Halides Catalyzed by BINAP-Ligated Palladium Complexes. J. Am. Chem. Soc. 2006, 128, 3584–3591. 10.1021/ja045533c. [DOI] [PubMed] [Google Scholar]
  32. Shekhar S.; Hartwig J. F. Effects of Bases and Halides on the Amination of Chloroarenes Catalyzed by Pd(PtBu3)2. Organometallics 2007, 26, 340–351. 10.1021/om0607548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hoi K. H.; Çalimsiz S.; Froese R. D. J.; Hopkinson A. C.; Organ M. G. Amination with Pd-NHC Complexes: Rate and Computational Studies Involving Substituted Aniline Substrates. Chem. - Eur. J. 2012, 18, 145–151. 10.1002/chem.201102428. [DOI] [PubMed] [Google Scholar]
  34. Cundari T. R.; Deng J. Density Functional Theory Study of Palladium-Catalyzed Aryl-Nitrogen and Aryl-Oxygen Bond Formation. J. Phys. Org. Chem. 2005, 18, 417–425. 10.1002/poc.889. [DOI] [Google Scholar]
  35. McMullin C. L.; Rühle B.; Besora M.; Orpen A. G.; Harvey J. N.; Fey N. Computational Study of PtBu3 as Ligand in the Palladium-Catalysed Amination of Phenylbromide with Morpholine. J. Mol. Catal. A: Chem. 2010, 324, 48–55. 10.1016/j.molcata.2010.02.030. [DOI] [Google Scholar]
  36. Sunesson Y.; Limé E.; Lill S. O. N.; Meadows R. E.; Norrby P.-O. Role of the Base in Buchwald–Hartwig Amination. J. Org. Chem. 2014, 79, 11961–11969. 10.1021/jo501817m. [DOI] [PubMed] [Google Scholar]
  37. Yong F. F.; Mak A. M.; Wu W.; Sullivan M. B.; Robins E. G.; Johannes C. W.; Jong H.; Lim Y. H. Empirical and Computational Insights into N-Arylation Reactions Catalyzed by Palladium meta-Terarylphosphine Catalyst. ChemPlusChem 2017, 82, 750–757. 10.1002/cplu.201700042. [DOI] [PubMed] [Google Scholar]
  38. Kim S.-T.; Pudasaini B.; Baik M.-H. Mechanism of Palladium-Catalyzed C–N Coupling with 1,8-Diazabicyclo[5.4.0]Undec-7-Ene (DBU) as a Base. ACS Catal. 2019, 9, 6851–6856. 10.1021/acscatal.9b02373. [DOI] [Google Scholar]
  39. Gómez-Orellana P.; Lledós A.; Ujaque G. Computational Analysis on the Pd-Catalyzed C–N Coupling of Ammonia with Aryl Bromides Using a Chelate Phosphine Ligand. J. Org. Chem. 2021, 86, 4007–4017. 10.1021/acs.joc.0c02865. [DOI] [PubMed] [Google Scholar]
  40. Christmann U.; Vilar R. Monoligated Palladium Species as Catalysts in Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2005, 44, 366–374. 10.1002/anie.200461189. [DOI] [PubMed] [Google Scholar]
  41. Zheng Q.; Liu Y.; Chen Q.; Hu M.; Helmy R.; Sherer E. C.; Welch C. J.; Chen H. Capture of Reactive Monophosphine-Ligated Palladium(0) Intermediates by Mass Spectrometry. J. Am. Chem. Soc. 2015, 137, 14035–14038. 10.1021/jacs.5b08905. [DOI] [PubMed] [Google Scholar]
  42. Firsan S. J.; Sivakumar V.; Colacot T. J. Emerging Trends in Cross-Coupling: Twelve-Electron-Based L1Pd(0) Catalysts, Their Mechanism of Action, and Selected Applications. Chem. Rev. 2022, 122, 16983–17027. 10.1021/acs.chemrev.2c00204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Balcells D.; Nova A. Designing Pd and Ni Catalysts for Cross-Coupling Reactions by Minimizing Off-Cycle Species. ACS Catal. 2018, 8, 3499–3515. 10.1021/acscatal.8b00230. [DOI] [Google Scholar]
  44. Li H.; Seechurn C. C. C. J.; Colacot T. J. Development of Preformed Pd Catalysts for Cross-Coupling Reactions, Beyond the 2010 Nobel Prize. ACS Catal. 2012, 2, 1147–1164. 10.1021/cs300082f. [DOI] [Google Scholar]
  45. Wei C. S.; Davies G. H. M.; Soltani O.; Albrecht J.; Gao Q.; Pathirana C.; Hsiao Y.; Tummala S.; Eastgate M. D. The Impact of Palladium(II) Reduction Pathways on the Structure and Activity of Palladium(0) Catalysts. Angew. Chem., Int. Ed. 2013, 52, 5822–5826. 10.1002/anie.201210252. [DOI] [PubMed] [Google Scholar]
  46. Hazari N.; Melvin P. R.; Beromi M. M. Well-Defined Nickel and Palladium Precatalysts for Cross-Coupling. Nat. Rev. Chem. 2017, 1, 0025 10.1038/s41570-017-0025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Shaughnessy K. H. Development of Palladium Precatalysts That Efficiently Generate LPd(0) Active Species. Isr. J. Chem. 2020, 60, 180–194. 10.1002/ijch.201900067. [DOI] [Google Scholar]
  48. Hruszkewycz D. P.; Balcells D.; Guard L. M.; Hazari N.; Tilset M. Insight into the Efficiency of Cinnamyl-Supported Precatalysts for the Suzuki–Miyaura Reaction: Observation of Pd(I) Dimers with Bridging Allyl Ligands During Catalysis. J. Am. Chem. Soc. 2014, 136, 7300–7316. 10.1021/ja412565c. [DOI] [PubMed] [Google Scholar]
  49. Seechurn C. C. C. J.; Parisel S. L.; Colacot T. J. Air-Stable Pd(R-Allyl)LCl (L= Q-Phos, P(t-Bu)3, Etc.) Systems for C–C/N Couplings: Insight into the Structure–Activity Relationship and Catalyst Activation Pathway. J. Org. Chem. 2011, 76, 7918–7932. 10.1021/jo2013324. [DOI] [PubMed] [Google Scholar]
  50. For allyl-Pd(II) precatalysts that do not form unreactive bridged-allyl Pd(I) dimers see:; a Melvin P. R.; Nova A.; Balcells D.; Dai W.; Hazari N.; Hruszkewycz D. P.; Shah H. P.; Tudge M. T. Design of a Versatile and Improved Precatalyst Scaffold for Palladium-Catalyzed Cross-Coupling: (η3-1-tBu-Indenyl)2(μ-Cl)2Pd2. ACS Catal. 2015, 5, 3680–3688. 10.1021/acscatal.5b00878. [DOI] [Google Scholar]; b Sivendran N.; Pirkl N.; Hu Z.; Doppiu A.; Gooβen L. J. Halogen-Bridged Methylnaphthyl Palladium Dimers as Versatile Catalyst Precursors in Coupling Reactions. Angew. Chem., Int. Ed. 2021, 60, 25151–25160. 10.1002/anie.202110450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. For the application of Pd(I) dimers as precatalysts in cross-coupling reactions see:; a Reference 42.; b Fricke C.; Sperger T.; Mendel M.; Schoenebeck F. Catalysis with Palladium(I) Dimers. Angew. Chem., Int. Ed. 2021, 60, 3355–3366. 10.1002/anie.202011825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Kinzel T.; Zhang Y.; Buchwald S. L. A New Palladium Precatalyst Allows for the Fast Suzuki–Miyaura Coupling Reactions of Unstable Polyfluorophenyl and 2-Heteroaryl Boronic Acids. J. Am. Chem. Soc. 2010, 132, 14073–14075. 10.1021/ja1073799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Bruno N. C.; Tudge M. T.; Buchwald S. L. Design and Preparation of New Palladium Precatalysts for C–C and C–N Cross-Coupling Reactions. Chem. Sci. 2013, 4, 916–920. 10.1039/C2SC20903A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Bruneau A.; Roche M.; Alami M.; Messaoudi S. 2-Aminobiphenyl Palladacycles: The “Most Powerful” Precatalysts in C–C and C–Heteroatom Cross-Couplings. ACS Catal. 2015, 5, 1386–1396. 10.1021/cs502011x. [DOI] [Google Scholar]
  55. Bruno N. C.; Buchwald S. L. Synthesis and Application of Palladium Precatalysts That Accommodate Extremely Bulky Di-tert-butylphosphino Biaryl Ligands. Org. Lett. 2013, 15, 2876–2879. 10.1021/ol401208t. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Park N. H.; Vinogradova E. V.; Surry D. S.; Buchwald S. L. Design of New Ligands for the Palladium-Catalyzed Arylation of α-Branched Secondary Amines. Angew. Chem., Int. Ed. 2015, 54, 8259–8262. 10.1002/anie.201502626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. DeAngelis A. J.; Gildner P. G.; Chow R.; Colacot T. J. Generating Active “L-Pd(0)” via Neutral or Cationic π-Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic, and Structure–Activity Studies in Challenging Cross-Coupling Reactions. J. Org. Chem. 2015, 80, 6794–6813. 10.1021/acs.joc.5b01005. [DOI] [PubMed] [Google Scholar]
  58. Thakore R. R.; Takale B. S.; Gallou F.; Reilly J.; Lipshutz B. H. N,C-Disubstituted Biarylpalladacycles as Precatalysts for ppm Pd-Catalyzed Cross Couplings in Water under Mild Conditions. ACS Catal. 2019, 9, 11647–11657. 10.1021/acscatal.9b04204. [DOI] [Google Scholar]
  59. Ortega-Moreno L.; Fernández-Espada M.; Moreno J. J.; Navarro-Gilabert C.; Campos J.; Conejero S.; López-Serrano J.; Maya C.; Peloso R.; Carmona E. Synthesis, Properties, and Some Rhodium, Iridium, and Platinum Complexes of a Series of Bulky m-Terphenylphosphine Ligands. Polyhedron 2016, 116, 170–181. 10.1016/j.poly.2016.04.023. [DOI] [Google Scholar]
  60. Marín M.; Moreno J. J.; Navarro-Gilabert C.; Álvarez E.; Maya C.; Peloso R.; Nicasio M. C.; Carmona E. Synthesis, Structure and Nickel Carbonyl Complexes of Dialkylterphenyl Phosphines. Chem. - Eur. J. 2019, 25, 260–272. 10.1002/chem.201803598. [DOI] [PubMed] [Google Scholar]
  61. Marín M.; Moreno J. J.; Alcaide M. M.; Álvarez E.; López-Serrano J.; Campos J.; Nicasio M. C.; Carmona E. Evaluating Stereoelectronic Properties of Bulky Dialkylterphenyl Phosphine Ligands. J. Organomet. Chem. 2019, 896, 120–128. 10.1016/j.jorganchem.2019.06.003. [DOI] [Google Scholar]
  62. Rama R. J.; Maya C.; Nicasio M. C. Dialkylterphenyl Phosphine-Based Palladium Precatalysts for Efficient Aryl Amination of N-Nucleophiles. Chem. - Eur. J. 2020, 26, 1064–1073. 10.1002/chem.201903279. [DOI] [PubMed] [Google Scholar]
  63. Monti A.; Rama R. J.; Gómez B.; Maya C.; Álvarez E.; Carmona E.; Nicasio M. C. N-Substituted Aminobiphenyl Palladacycles Stabilized by Dialkylterphenyl Phosphanes: Preparation and Applications in C-N Cross-Coupling Reactions. Inorg. Chim. Acta 2021, 518, 120214 10.1016/j.ica.2020.120214. [DOI] [Google Scholar]
  64. Biscoe M. R.; Fors B. P.; Buchwald S. L. A New Class of Easily Activated Palladium Precatalysts for Facile C–N Cross-Coupling Reactions and the Low Temperature Oxidative Addition of Aryl Chlorides. J. Am. Chem. Soc. 2008, 130, 6686–6687. 10.1021/ja801137k. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Bruno N. C.; Niljianskul N.; Buchwald S. L. N-Substituted 2-Aminobiphenylpalladium Methanesulfonate Precatalysts and Their Use in C–C and C–N Cross-Couplings. J. Org. Chem. 2014, 79, 4161–4166. 10.1021/jo500355k. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Calculations using the cluster model to simulate an intermolecular deprotonation pathway led to convergence problems. The precatalyst activation was also studied with tert-butoxide anion as the base yielding low energy barriers (see Supporting Information for details).
  67. Driver M. S.; Hartwig J. F. A Rare, Low-Valent Alkylamido Complex, a Diphenylamido Complex, and Their Reductive Elimination of Amines by Three-Coordinate Intermediates. J. Am. Chem. Soc. 1995, 117, 4708–4709. 10.1021/ja00121a030. [DOI] [Google Scholar]
  68. Kapdi A. R.; Whitwood A. C.; Williamson D. C.; Lynam J. M.; Burns M. J.; Williams T. J.; Reay A. J.; Holmes J.; Fairlamb I. J. S. The Elusive Structure of Pd2(dba)3. Examination by Isotopic Labeling, NMR Spectroscopy, and X-Ray Diffraction Analysis: Synthesis and Characterization of Pd2(dba-Z)3 Complexes. J. Am. Chem. Soc. 2013, 135, 8388–8399. 10.1021/ja403259c. [DOI] [PubMed] [Google Scholar]
  69. Singh U. K.; Strieter E. R.; Blackmond D. G.; Buchwald S. L. Mechanistic Insights into the Pd(BINAP)-Catalyzed Amination of Aryl Bromides: Kinetic Studies under Synthetically Relevant Conditions. J. Am. Chem. Soc. 2002, 124, 14104–14114. 10.1021/ja026885r. [DOI] [PubMed] [Google Scholar]
  70. Ingoglia B. T.; Wagen C. C.; Buchwald S. L. Biaryl Monophosphine Ligands in Palladium-Catalyzed C–N Coupling: An Updated User’s Guide. Tetrahedron 2019, 75, 4199–4211. 10.1016/j.tet.2019.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Yin J.; Rainka M. P.; Zhang X.-X.; Buchwald S. L. A Highly Active Suzuki Catalyst for the Synthesis of Sterically Hindered Biaryls: Novel Ligand Coordination. J. Am. Chem. Soc. 2002, 124, 1162–1163. 10.1021/ja017082r. [DOI] [PubMed] [Google Scholar]
  72. Walker S. D.; Barder T. E.; Martinelli J. R.; Buchwald S. L. A Rationally Designed Universal Catalyst for Suzuki–Miyaura Coupling Processes. Angew. Chem., Int. Ed. 2004, 43, 1871–1876. 10.1002/anie.200353615. [DOI] [PubMed] [Google Scholar]
  73. Barder T. E.; Walker S. D.; Martinelli J. R.; Buchwald S. L. Catalysts for Suzuki–Miyaura Coupling Processes: Scope and Studies of the Effect of Ligand Structure. J. Am. Chem. Soc. 2005, 127, 4685–4696. 10.1021/ja042491j. [DOI] [PubMed] [Google Scholar]
  74. Herrmann W. A.; Thiel W. R.; Broißmer C.; Öfele K.; Priermeier T.; Scherer W. Dihalogenmethyl)Palladium(II)-Komplexe aus Palladium(O)-Vorstufen des Dibenzylidenacetons: Synthese, Strukturchemie und Reaktivität. J. Organomet. Chem. 1993, 461, 51–60. 10.1016/0022-328X(93)83273-X. [DOI] [Google Scholar]
  75. Tschoerner M.; Trabesinger G.; Albinati A.; Pregosin P. S. New Chiral Complexes of Palladium(0) Containing P,S- and P,P-Bidentate Ligands. Organometallics 1997, 16, 3447–3453. 10.1021/om970185r. [DOI] [Google Scholar]
  76. Harding B. A.; Melvin P. R.; Dougherty W.; Kassel S.; Goodson F. E. Capturing a Ghost. Synthesis and Structural Characterization of Pd(dba)[P(o-Tol)3]2. Organometallics 2013, 32, 3570–3573. 10.1021/om400335a. [DOI] [Google Scholar]
  77. Bei X.; Turner H. W.; Weinberg W. H.; Guram A. S.; Petersen J. L. Palladium/P,O-Ligand-Catalyzed Suzuki Cross-Coupling Reactions of Arylboronic Acids and Aryl Chlorides. Isolation and Structural Characterization of (P,O)-Pd(dba) Complex. J. Org. Chem. 1999, 64, 6797–6803. 10.1021/jo990805t. [DOI] [PubMed] [Google Scholar]
  78. Scharf L. T.; Rodstein I.; Schmidt M.; Scherpf T.; Gessner V. H. Unraveling the High Activity of Ylide-Functionalized Phosphines in Palladium-Catalyzed Amination Reactions: A Comparative Study with CyJohnPhos and PtBu3. ACS Catal. 2020, 10, 999–1009. 10.1021/acscatal.9b04666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Senn H. M.; Ziegler T. Oxidative Addition of Aryl Halides to Palladium(0) Complexes: A Density-Functional Study Including Solvation. Organometallics 2004, 23, 2980–2988. 10.1021/om049963n. [DOI] [Google Scholar]
  80. Barder T. E.; Biscoe M. R.; Buchwald S. L. Structural Insights into Active Catalyst Structures and Oxidative Addition to (Biaryl)Phosphine–Palladium Complexes via Density Functional Theory and Experimental Studies. Organometallics 2007, 26, 2183–2192. 10.1021/om0701017. [DOI] [Google Scholar]
  81. Ahlquist M.; Norrby P.-O. Oxidative Addition of Aryl Chlorides to Monoligated Palladium(0): A DFT-SCRF Study. Organometallics 2007, 26, 550–553. 10.1021/om0604932. [DOI] [Google Scholar]
  82. Fors B. P.; Watson D. A.; Biscoe M. R.; Buchwald S. L. A Highly Active Catalyst for Pd-Catalyzed Amination Reactions: Cross-Coupling Reactions Using Aryl Mesylates and the Highly Selective Monoarylation of Primary Amines Using Aryl Chlorides. J. Am. Chem. Soc. 2008, 130, 13552–13554. 10.1021/ja8055358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Milner P. J.; Maimone T. J.; Su M.; Chen J.; Müller P.; Buchwald S. L. Investigating the Dearomative Rearrangement of Biaryl Phosphine-Ligated Pd(II) Complexes. J. Am. Chem. Soc. 2012, 134, 19922–19934. 10.1021/ja310351e. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Rama R. J.; Maya C.; Nicasio M. C. Palladium-mediated intramolecular dearomatization of ligated dialkylterphenyl phosphines. Dalton Trans. 2019, 48, 14575–14579. 10.1039/C9DT03201K. [DOI] [PubMed] [Google Scholar]; X-ray structural characterization of 3OMe was reported.
  85. Falceto A.; Carmona E.; Alvarez S. Electronic and Structural Effects of Low-Hapticity Coordination of Arene Rings to Transition Metals. Organometallics 2014, 33, 6660–6668. 10.1021/om5009583. [DOI] [Google Scholar]
  86. Yamashita M.; Hartwig J. F. Synthesis, Structure, and Reductive Elimination Chemistry of Three-Coordinate Arylpalladium Amido Complexes. J. Am. Chem. Soc. 2004, 126, 5344–5345. 10.1021/ja0315107. [DOI] [PubMed] [Google Scholar]
  87. A Pd(II) phenoxide complex stabilized by a monophophine ligand was identified as a resting state of the catalyst in the coupling of fluoroalkylamines with aryl halides: see reference 14
  88. Widenhoefer R. A.; Zhong H. A.; Buchwald S. L. Synthesis and Solution Structure of Palladium Tris(o-tolyl)phosphine Mono(Amine) Complexes. Organometallics 1996, 15, 2745–2754. 10.1021/om9509599. [DOI] [Google Scholar]
  89. Widenhoefer R. A.; Buchwald S. L. Halide and Amine Influence in the Equilibrium Formation of Palladium Tris(o-tolyl)phosphine Mono(amine) Complexes from Palladium Aryl Halide Dimers. Organometallics 1996, 15, 2755–2763. 10.1021/om9509608. [DOI] [Google Scholar]
  90. Driver M. S.; Hartwig J. F. Carbon–Nitrogen-Bond-Forming Reductive Elimination of Arylamines from Palladium(II) Phosphine Complexes. J. Am. Chem. Soc. 1997, 119, 8232–8245. 10.1021/ja971057x. [DOI] [Google Scholar]
  91. Hartwig J. F. Electronic Effects on Reductive Elimination To Form Carbon–Carbon and Carbon–Heteroatom Bonds from Palladium(II) Complexes. Inorg. Chem. 2007, 46, 1936–1947. 10.1021/ic061926w. [DOI] [PubMed] [Google Scholar]
  92. Bordwell F. G.; Drucker G. E.; Fried H. E. Acidities of carbon and nitrogen acids: the aromaticity of the cyclopentadienyl anion. J. Org. Chem. 1981, 46, 632–635. 10.1021/jo00316a032. [DOI] [Google Scholar]
  93. Besora M.; Maseras F. Microkinetic Modeling in Homogeneous Catalysis. WIREs Comput. Mol. Sci. 2018, 8, e1372 10.1002/wcms.1372. [DOI] [Google Scholar]
  94. Jaraíz M.DFT-Based Microkinetic Simulations: A Bridge Between Experiment and Theory in Synthetic Chemistry. In Topics in Organometallic Chemistry; Springer Science and Business Media Deutschland GmbH, 2020; Vol. 67, pp 81–105. [Google Scholar]
  95. Jaraíz M.; Rubio J. E.; Enríquez L.; Pinacho R.; López-Pérez J. L.; Lesarri A. An Efficient Microkinetic Modeling Protocol: Start with Only the Dominant Mechanisms, Adjust All Parameters, and Build the Complete Model Incrementally. ACS Catal. 2019, 9, 4804–4809. 10.1021/acscatal.9b00522. [DOI] [Google Scholar]
  96. Suàrez L. A.; Culakova Z.; Balcells D.; Bernskoetter W. H.; Eisenstein O.; Goldberg K. I.; Hazari N.; Tilset M.; Nova A. The Key Role of the Hemiaminal Intermediate in the Iron-Catalyzed Deaminative Hydrogenation of Amides. ACS Catal. 2018, 8, 8751–8762. 10.1021/acscatal.8b02184. [DOI] [Google Scholar]
  97. Salamanca V.; Albéniz A. C. Faster Palladium-Catalyzed Arylation of Simple Arenes in the Presence of a Methylketone: Beneficial Effect of an a Priori Interfering Solvent in C–H Activation. Org. Chem. Front. 2021, 8, 1941–1951. 10.1039/D1QO00236H. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

cs3c00075_si_001.pdf (3.1MB, pdf)
cs3c00075_si_002.cif (986.5KB, cif)
cs3c00075_si_003.cif (1.6MB, cif)
cs3c00075_si_004.cif (1.5MB, cif)
cs3c00075_si_005.xyz (502.4KB, xyz)

Articles from ACS Catalysis are provided here courtesy of American Chemical Society

RESOURCES