Characterization of DMSO Coordination to Palladium(II) in Solution and Insights into the Aerobic Oxidation Catalyst, Pd(DMSO)₂(TFA)₂

Abstract

Recent studies have shown that Pd(DMSO)₂(TFA)₂ (TFA = trifluoroacetate) is an effective catalyst for a number of different aerobic oxidation reactions. Here, we provide insights into the coordination properties of DMSO to palladium(II) in both the solid state and in solution. A crystal structure of Pd(DMSO)₂(TFA)₂ confirms that the solid-state structure of this species has one O-bound and one S-bound DMSO ligand, and a crystallographically characterized mono-DMSO complex, trans-Pd(DMSO)(OH₂)(TFA)₂, exhibits an S-bound DMSO ligand. ¹H and ¹⁹F NMR spectroscopic studies show that, in EtOAc and THF-d₈, Pd(DMSO)₂(TFA)₂ consists of an equilibrium mixture of Pd(S-DMSO)(O-DMSO)(TFA)₂ and Pd(S-DMSO)₂(TFA)₂. The O-bound DMSO is determined to be more labile than the S-bound DMSO ligand, and both DMSO ligands are more labile in THF relative to EtOAc as the solvent. DMSO coordination to Pd^II is substantially less favorable when the TFA ligands are replaced with acetate. An analogous carboxylate ligand effect is observed in the coordination of Pd^II to the bidentate sulfoxide ligand, 1,2-bis(phenylsulfinyl)ethane. DMSO coordination to Pd(TFA)₂ is shown to be incomplete in AcOH-d₄ and toluene-d₈, resulting in Pd^II/DMSO adducts with < 2:1 DMSO:Pd^II stoichiometry. Collectively, these results provide useful insights into the coordination properties of DMSO to Pd^II under catalytically relevant conditions.

Introduction

A number of homogeneous palladium catalysts have been developed over the past decade for selective aerobic oxidation of organic molecules.¹ One of the earliest reported catalyst systems consists of Pd(OAc)₂ in DMSO as the solvent, which was first reported by the groups of Larock and Hiemstra in the mid-1990s.² This simple catalyst system has been used in a variety of oxidative transformations, including alcohol oxidation, intramolecular hetero- and carbocyclization of alkenes, and cycloalkenylation of silyl enol ethers.³ In these reactions, DMSO has been proposed to serve as a ligand and is believed to play a vital role in stabilizing Pd⁰ and promoting the reoxidation of Pd⁰ by O₂.⁴ Characterization of the coordination properties of DMSO in these reactions is complicated by the large excess of DMSO and insights thus far have been limited to computational studies.⁵

Sulfoxides, including DMSO and bis-sulfoxides, have been used as ligands or additives to promote a variety of Pd-catalyzed oxidation reactions, often using benzoquinone or Ag^I as the stoichiometric oxidants.⁶ Recently, we have reported that Pd(DMSO)₂(TFA)₂, in which DMSO is present in catalytic quantities, is an effective catalyst system for a number of oxidation reactions capable of using O₂ as the oxidant, including α,β-dehydrogenation of carbonyl compounds (eq 1)⁷ and oxidative amination of alkenes (eqs 2 and 3).⁸ A similar catalyst system has been reported by Buchwald and coworkers for chelate-directed C–H arylation of anilides (eq 4).⁹ Pd(TFA)₂ (TFA = trifluroacetate) was the palladium source for dehydrogenation reactions and oxidative amination, while Pd(OAc)₂ in combination with trifluoroacetic acid was used as the catalyst in the biaryl-coupling reaction.

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The coordination chemistry of DMSO to late transition metals has been the subject of considerable investigation.¹⁰ Depending on the identity of the metal and other ancillary ligands, DMSO can exhibit S-, O- or bridging μ–S,O-bound coordination modes. Soft metals, such as Ru^II, Os^II, Rh^I and Pt^II, typically favor DMSO coordination via the sulfur atom, but O-coordination has also been observed.¹⁰ Representative d⁸ metal-DMSO complexes include [Rh(S-DMSO)₂(O-DMSO)₂][PF₆],¹¹ [Pt(bpy)(S-DMSO)Cl][BF₄] (bpy = 2,2′-bipyridine) and [Pd(phen)-(O-DMSO)Cl][PF₆] (phen = phenanthroline).¹² IR and ¹H NMR spectroscopic methods provide a valuable complement to X-ray crystallography in establishing the coordination mode of DMSO to transition metals.^10,13 In the aforementioned complexes, S-coordinated DMSO ligands exhibit S–O stretching frequencies that range from 1080 to 1154 cm⁻¹, while O-bound DMSO ligands exhibit lower vibrational frequencies, ranging from 862 to 997 cm⁻¹ (Table 1). In the ¹H NMR spectra, S-bound DMSO ligands exhibit ¹H NMR chemical shifts approximately 1 ppm downfield relative to free DMSO (~2.53 ppm), whereas O-bound DMSO exhibits a smaller downfield shift (Table 1).¹⁴

Table 1.

IR and ¹H NMR Spectroscopic Data of DMSO and Transition Metal-coordinated DMSO Reported in the Literature¹⁰

	IR (S–O) (cm−1)	1H NMR (ppm)
Free DMSO	1005	~ 2.53
S-DMSO ligands	1080 – 1154	3.80 – 3.30
O-DMSO ligands	862 – 997	3.03 – 2.59

Pd^II complexes have been identified with both S- and O-DMSO coordination. For example, in Pd(DMSO)₂Cl₂ both DMSO ligands are S-bound, ¹⁵ whereas [Pd(phen)(O-DMSO)Cl][PF₆] features an O-bound DMSO.¹² Complexes containing both S- and O-bound DMSO ligands are also known, including [Pd(DMSO)₄](BF₄)₂, which has two S-bound and two O-bound DMSO ligands.¹⁵

Pd(DMSO)₂(TFA)₂ was first characterized by IR spectroscopy in the solid state in 1965 by Wilkinson and coworkers,¹⁶ and the data provided evidence for S-bound DMSO. Cotton and coworkers then reported a crystal structure of this complex, which revealed the presence of trans-DMSO ligands, one S-bound and one O-bound.¹⁷ In light of the growing significance of DMSO-ligated Pd^II complexes in aerobic oxidation reactions and the difficulty in characterizing the DMSO coordination chemistry in DMSO solvent, we wanted to establish the coordination chemistry of Pd(DMSO)₂(TFA)₂ in solution. Here, we report the characterization of this complex by ¹H and ¹⁹F NMR spectroscopy in catalytically relevant solvents, EtOAc, THF, AcOH and toluene. The results are supplemented by X-ray crystallographic and IR spectroscopic data, and they provide valuable insights into the structure and dynamic properties of this complex in solution.

Results and Discussion

X-ray Crystal Structures of DMSO-Ligated Pd(TFA)₂ Complexes

Deep orange crystals were obtained from a solution of Pd(TFA)₂ and 2 equiv. of DMSO in EtOAc, and X-ray diffraction analysis established the structure of trans-Pd(S-DMSO)(O-DMSO)(TFA)₂ (Figure 1), which exhibits only slight variations relative to the structure originally reported by Cotton and workers.¹⁷ The S-bound DMSO ligand has a shorter S–O bond [1.4633(17) Å] and the O-bound DMSO ligand has a longer S–O bond [1.5509(16) Å] relative to that of free DMSO (1.52 Ź⁸). The solid-state infrared absorption spectrum of this complex reveals absorption bands at 1149 cm⁻¹ and 923 cm⁻¹. These bands, which are blue- and red-shifted relative to free DMSO, ν_S–O = 1005 cm⁻¹, correspond to the S–O stretching frequencies of the S- and O-bound DMSO ligands, respectively.¹⁹

Figure 1.

Molecular structure of Pd(S-DMSO)(O-DMSO)(TFA)₂, with 50% probability ellipsoids. Selected bond lengths, Å: Pd1-O1: 2.0158(15), Pd1-O3: 2.0170(16), Pd1-O6: 2.0554(16), Pd1-S1: 2.1994(5), S1-O5: 1.4633(17), S2-O6: 1.5509(16).

A mono-DMSO-ligated Pd^II complex was obtained from an EtOAc solution of Pd(TFA)₂ containing only 1 equiv. of DMSO. X-ray diffraction analysis established the structure of trans-Pd(S-DMSO)(OH₂)(TFA)₂ (Figure 2). The H₂O molecule, coordinated trans to the S-DMSO ligand, is hydrogen bonded to the carboxylates of adjacent molecules (see Supporting Information for details). An IR spectrum of the solid Pd(S-DMSO)(OH₂)(TFA)₂ exhibits an absorption band at 1155 cm⁻¹, consistent with S-coordination of DMSO (cf. Table 1). The lack of absorption bands between 860 and 1000 cm⁻¹ is consistent with the absence of an O-bound DMSO ligand.

Figure 2.

Molecular structure of Pd(S-DMSO)(OH₂)(TFA)₂, with 50% probability ellipsoids. The half molecule of co-crystallized solvent ethyl acetate is not shown. Selected bond lengths, Å: Pd1-O1: 2.0205(13), Pd1-O3: 2.0171(13), Pd1-O5: 2.0564(13), Pd1-S1: 2.1979(8), S1-O6: 1.4677(13).

The Solution-Phase Structure of Pd(TFA)₂/DMSO in EtOAc

(A) Spectroscopic Data

Discrepancies can exist between solid-state and solution structures of transition-metal complexes. For example, the DMSO ligand in [Pd(bpy)(DMSO)Cl][PF₆] (bpy = 2,2′-bipyridine) was determined to be O-bound by X-ray crystallography; however, a mixture of O- and S-DMSO ligated species was observed in CD₃NO₂ by ¹H NMR spectroscopy.¹² In order to probe the similarities and differences between solid-state and solution structures of Pd(TFA)₂/DMSO complexes, a combination of ¹H and ¹⁹F NMR spectroscopy was used to determine the coordination properties of DMSO to Pd^II in catalytically relevant solvents.

The Pd(TFA)₂/DMSO-catalyzed dehydrogenation of cyclohexanone was performed in EtOAc (eq 1), and our initial spectroscopic studies were carried out in this solvent.⁷ A titration experiment was carried out by adding DMSO to a solution of Pd(TFA)₂ in EtOAc-d₀. The initial titration experiments were performed at −60 °C in order to slow dynamic processes. Pd(TFA)₂ completely dissolves in EtOAc and no ¹H resonances are observed in the ¹H NMR spectrum between 2.3 and 3.7 ppm (Figure 3). Addition of 0.5 equiv. of DMSO relative to Pd results in the appearance of a singlet at 3.47 ppm. This peak grows upon addition of another 0.5 equiv. of DMSO (1 equiv. total), with concomitant formation of three new smaller peaks at 3.58, 3.42 and 2.95 ppm. Further addition of DMSO results in diminishment of the peak at 3.47 ppm and growth of the peaks at 3.58, 3.42 and 2.95 ppm. With 2 equiv. of DMSO, the peak at 3.47 ppm is not present, but a new peak at 3.08 ppm is evident.²⁰ A broad peak, corresponding to free DMSO, appears at 2.64 ppm and the peak at 2.95 ppm is broadened in the presence of 3 equiv. DMSO.

Figure 3.

¹H NMR spectra of Pd(TFA)₂ in EtOAc in the presence of various quantities of DMSO at –60 °C. Conditions: [Pd(TFA)₂] = 30 mM (6.6 mg, 0.02 mmol), EtOAc = 0.65 mL, –60 °C, [DMSO] = 0, 15, 30, 39, 48, 60 and 90 mM.

The same DMSO titration solutions were analyzed by ¹⁹F NMR spectroscopy (Figure 4). In EtOAc, Pd(TFA)₂ exhibits a singlet at –76.76 ppm. Multiple minor species are evident between –73.50 and –75.30 ppm, the integrations of which vary at different temperatures and Pd(TFA)₂ concentrations. A singlet at –74.74 ppm appears upon addition of 0.5 equiv. of DMSO. Further addition of DMSO leads to decreased integration of the Pd(TFA)₂ peak at –76.76 ppm, with concomitant growth of the peak at –74.74 ppm and appearance of two new singlets at –74.80 and –75.00 ppm. With 2 and 3 equiv. of DMSO, the peaks at –74.80 and –75.00 ppm are the sole peaks present in the ¹⁹F NMR spectrum.

Figure 4.

¹⁹F NMR spectra of Pd(TFA)₂ in EtOAc in the presence of various quantities of DMSO at –60 °C. Conditions: [Pd(TFA)₂] = 30 mM (6.6 mg, 0.02 mmol), EtOAc = 0.65 mL, –60 °C, [DMSO] = 0, 15, 30, 39, 48, 60 and 90 mM.

The temperature dependence of equilibra between different Pd(TFA)₂/DMSO complexes has been investigated with the sample containing 1.6 equiv. of DMSO, in which multiple species are evident in the NMR spectra. Both ¹H and ¹⁹F NMR spectra exhibit peak broadening as the temperature is increased (Figure 5). At temperatures above –20 °C, the ¹H peaks at 3.47 and 3.42 ppm coalesce into one peak with concomitant broadening of the peak at 2.95 ppm. Similar coalescence occurs for the ¹⁹F peaks at –74.74 and –74.80 ppm. In contrast, the ¹H peak at 3.58 ppm and ¹⁹F peak at –75.00 ppm remain sharp throughout the temperature range.

Figure 5.

NMR spectra of Pd(TFA)₂/DMSO (1:1.6) in EtOAc at various temperatures. (A) ¹H NMR spectra; (B) ¹⁹F NMR spectra. Conditions: [Pd(TFA)₂] = 30 mM (6.6 mg, 0.02 mmol), [DMSO] = 48 mM (1.6 equiv.), EtOAc = 0.65 mL, T = –60, –50, –40, –20, 0 and 24 °C.

(B) Structural Assignments

Assignments of the peaks in the ¹H NMR spectra presented above are facilitated by the literature precedents, and peaks in the ¹⁹F NMR spectra may be correlated to those in the ¹H NMR spectra and assigned accordingly. The solid-state structure of Pd(TFA)₂ is trimeric; ²¹ however, Wilkinson has reported osmometry data suggesting that Pd(TFA)₂ dissociates into a monomer 1 in EtOAc (eq 5).¹⁶ The peak that appears at 3.47 ppm upon addition of DMSO is assigned to an S-bound DMSO ligand by analogy to previously characterized S-DMSO ligands (cf. Table 1), and integration of this peak and the corresponding new TFA peak in the ¹⁹F NMR spectrum at –74.74 ppm relative to an internal standard (C₆H₅F) reflects formation of a 1:1 DMSO:Pd(TFA)₂ complex (2a, eq 6), analogous to Pd(S-DMSO)(OH₂)(TFA)₂ (cf. Figure 2). An S-DMSO-ligated Pd(TFA)₂ dimer, such as 2b, is an alternative possible structure, particularly in light of analogous crystallographically characterized structures, [Pd(S-DMSO)(OAc)₂]₂ ²² and the phenylsulfoxide-ligated Pd(TFA)₂ dimer (Scheme 1).^23,24

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Scheme 1.

Dimeric Carboxylate-Bridged Pd^II Complexes Reported in the Literature^22,23

The peaks that appear in the ¹H and ¹⁹F NMR spectra upon addition of ≥ 1 equiv. of DMSO are consistent with bis-DMSO-coordinated Pd species. The ¹H peaks at 3.54 ppm and 3.42 ppm represent two different S-bound DMSO ligands, whereas the peak at 2.95 ppm is consistent with an O-bound DMSO ligand. The ¹H resonances at 3.42 ppm and 2.95 ppm correlate with the peak at ≥74.80 ppm in the ¹⁹F NMR spectra, and their respective integrations correspond to a ligand ratio of 1 S-DMSO : 1 O-DMSO : 2 TFA, consistent with the assignment of this species as Pd(S-DMSO)(O-DMSO)(TFA)₂ 3a (eq 7). The remaining S-bound DMSO peak at 3.58 ppm correlates with an ¹⁹F peak at –75.00 ppm, and integrations of these peaks correspond to a 1:1 DMSO : TFA ligand ratio. This complex is assigned as Pd(S-DMSO)₂(TFA)₂ 3b, in which both DMSO ligands coordinate via the sulfur atom (eq 7). Both cis and trans geometries of bis-(S-DMSO) Pd^II and Pt^II complexes are known.^25,26 Examples include trans-Pd(S-DMSO)₂Cl₂^25a trans-Pd(S-DMSO)₂(Ar)(TFA) (Ar = 2,4,5-(MeO)₃C₆H₂)^6d and cis-Pd(S-DMSO)₂(NO₃)₂.^26b We speculate that 3b has a trans geometry because it originates from displacement of the solvent ligand in trans-Pd(S-DMSO)(sol)(TFA)₂ 2a. Moreover, DFT calculations indicate that the trans geometry is more stable than the cis geometry by 2.6 kcal/mol.²⁷

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Based on above assignments, the ¹H and ¹⁹F NMR data can be used to plot the concentrations as a function of added DMSO (Figure 6), and the plot derived from the ¹H NMR spectra is in good agreement with that derived from the ¹⁹F NMR spectra. To summarize the results, initial addition of DMSO results in formation of a mono-DMSO-ligated Pd(TFA)₂ complex with DMSO coordinated via the S atom. Higher concentrations of DMSO leads to conversion of this species into an equilibrium mixture of bis-DMSO-ligated Pd(TFA)₂ complexes 3a and 3b. The bis-DMSO coordination to Pd^II is sufficiently favored that unbound DMSO is not evident until >2 equiv. of DMSO is added.

Figure 6.

Plots of Pd(TFA)₂/DMSO complexes present in solution as a function of added [DMSO] on the basis of ¹H and ¹⁹F NMR data, (A) and (B), respectively. Conditions: [Pd(TFA)₂] = 30 mM (6.6 mg, 0.02 mmol), EtOAc = 0.65 mL, –60 °C, [DMSO] = 0, 15, 30, 39, 48, 60 and 90 mM.

In the presence of 3 equiv. of DMSO, the significant line broadening is evident for the peaks corresponding to unbound DMSO and the O-bound DMSO ligand in 3a. This observation suggests that fast exchange takes place between them, and further implies that the O-bound DMSO ligand is more labile than the S-bound DMSO ligand. Complementary observations are obtained from the variable-temperature spectra of Pd(TFA)₂ in the presence of 1.6 equiv. of DMSO (Figure 5). This study reveals that 2a and 3a undergo fast exchange at elevated temperature (eq 8). Ligand exchange of the labile O-DMSO ligand in 3a with 2a, possibly catalyzed by the EtOAc solvent, can account for these observations. The kinetics of this exchange process will be discussed further below. The lack of peak broadening of 3b suggests that analogous exchange of the S-bound DMSO ligands in 3b does not take place on the NMR timescale.

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The temperature dependence plots shown in Figure S8 also reveal that the concentration of 3b decreased with concomitant increase of 3a at increased temperature, indicating a temperature-dependent equilibrium between 3a and 3b (eq 9). The equilibrium constants at various temperatures are calculated based on the ¹⁹F NMR spectra. van’t Hoff analysis reveals a linear relationship between the ln(K_eq) and 1/T (Figure S9) and enables determination of ΔH and ΔS, (– 2.7 kcal/mol and –13 e.u., respectively). The relatively large negative ΔS suggests that 3b has a more ordered structure than 3a.

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The catalytic oxidation of cyclohexanone in EtOAc employs Pd(TFA)₂ with 2 equiv. of DMSO at 60 °C. The data presented above suggest that only bis-DMSO coordinated Pd compounds 3a and 3b are present under these conditions. At 60 °C, significant peak broadening is observed among all species (data not shown), suggesting that fast exchange can take place between both S- and O-bound DMSO ligands at this temperature. The equilibrium constant between 3a and 3b was calculated to be 0.17 at 60 °C, based on the van’t Hoff analysis described above (eq 9). Therefore, under the catalytic condition of dehydrogenation, 3a is favored over 3b by a 6:1 ratio.

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Effect of the Anionic Ligand: Coordination Chemistry of DMSO to Pd(OAc)₂ in EtOAc

The use of trifluoroacetate as an anionic ligand is important to the success of the Pd/DMSO catalyst systems in eqs 1-3;^7,8 replacement of Pd(TFA)₂ with Pd(OAc)₂ has been shown to result in decreased yields. These observations prompted us to analyze the coordination chemistry of DMSO to Pd(OAc)₂ in EtOAc.

Pd(OAc)₂ fully dissolves in EtOAc to form an orange solution. Titration of DMSO into the solution results in the appearance of two broad peaks at 3.50 and 3.43 ppm in the ¹H NMR spectra, consistent with S-bound DMSO ligands, together with a peak at 2.60 ppm corresponding to free DMSO (Figure 7). Further addition of DMSO increases the concentration of bound DMSO ligands; however, the sum of the bound DMSO ligands maximizes at a DMSO:Pd^II ratio of approximately 2:3, when ≥ 10 equiv. of DMSO have been added (Figure 8).

Figure 7.

¹H NMR spectra of Pd(OAc)₂ in EtOAc with various quantities of DMSO at 24 °C. Conditions: [Pd(OAc)₂] = 30 mM (4.4 mg, 0.02 mmol), EtOAc = 0.65 mL, 24 °C, [DMSO] = 0, 7.5, 15 and 30 mM.

Figure 8.

Titration curves of DMSO into the solution of Pd(OAc)₂ in EtOAc at 24 °C. Conditions: [Pd(OAc)₂] = 30 mM (4.4 mg, 0.02 mmol), EtOAc = 0.65 mL, 24 °C, [DMSO] = 0, 15, 30, 60, 120, 300 and 600 mM.

The solid state structures of Pd(TFA)₂ and Pd(OAc)₂ have both been characterized previously to be trimeric by X-ray crystallography,²¹ and Pd(OAc)₂ has been proposed to remain trimeric in EtOAc.¹⁶ The 2:3 DMSO:Pd^II stoichiometry evident from the titration experiments in Figure 8 suggests that DMSO coordination might partially cleave the trimeric Pd(OAc)₂ structure forming linear trimers, such as complexes 5a and 5b (eq 11). A number of structurally similar acetatebridged trimeric Pd complexes have been reported previously in the literature. ²⁸ If this assignment is correct, the two distinct ¹H signals could arise from the C_s and C₂ isomers, 5a and 5b.

Despite the tentative nature of the Pd(OAc)₂/DMSO structural assignments, a distinction between DMSO coordination to Pd(TFA)₂ and Pd(OAc)₂ is clearly evident. The differences presumably reflect the different basicity of the carboxylate ligands. The more-basic acetate ligand should be a more effective bridging ligand, and cleavage of the trimeric structure by DMSO will be less favored. Such effects undoubtedly contribute to the different activities of Pd(TFA)₂ and Pd(OAc)₂ in the catalytic reactions. More detailed understanding of the catalytic implications of these observations requires further investigation.

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The Solution Phase Structure of Pd(TFA)₂/DMSO in THF-d₈

Pd(DMSO)₂(TFA)₂ in THF serves as an effective catalyst for oxidative amination reactions (eq 2),⁸ and we performed DMSO titration experiments similar to those described above with a solution of Pd(TFA)₂ in THF-d₈. The spectra reveal trends similar to those observed in EtOAc, as well as differences associated with dynamics of the exchange processes (Figures 9 and 10). Addition of 0.5 equiv. of DMSO leads to the appearance of a resonance at 3.29 ppm in the ¹H spectrum and a peak at –74.73 ppm in the ¹⁹F NMR spectrum. These peaks are assigned to the mono-DMSO complex 2a. Addition of more DMSO results in the appearance of peaks at 2.76 ppm and 3.35 ppm in the ¹H NMR spectra, and a peak at –74.97 ppm in the ¹⁹F NMR spectra. Meanwhile, the peak at 3.29 ppm in the ¹H NMR spectra and –74.73 ppm in the ¹⁹F NMR spectra shift upfield. Based upon the analysis of the EtOAc solutions, the peak at 3.35 ppm in the ¹H NMR spectra and –74.97 ppm in the ¹⁹F NMR spectra are assigned to Pd(S-DMSO)₂(TFA)₂, 3b. The peak at 2.76 ppm in the ¹H NMR spectra corresponds to an O-bound DMSO ligand, consistent with formation of Pd(S-DMSO)(O-DMSO)(TFA)₂, 3a.

Figure 9.

¹H NMR spectra of Pd(TFA)₂ in THF-d₈ with various quantities of DMSO at –60 °C. Conditions: [Pd(TFA)₂] = 15 mM (3.3 mg, 0.01 mmol), THF-d₈ = 0.65 mL, –60 °C, [DMSO] = 0, 7.5, 15, 19.5, 24, 30 and 60 mM.

Figure 10.

¹⁹F NMR spectra of Pd(TFA)₂ in THF-d₈ with various quantities of DMSO at –60 °C. Conditions: [Pd(TFA)₂] = 15 mM (3.3 mg, 0.01 mmol), THF-d₈ = 0.65 mL, –60 °C, [DMSO] = 0, 7.5, 15, 19.5, 24, 30 and 60 mM.

The S-bound DMSO ligand of 3a was not observed as an independent peak, but was manifested as an upfield shift of the S–bound DMSO resonance of 2a. This observation reflects fast exchange between 2a and 3a (cf. eq 8), resulting in coalescence of their S-bound DMSO resonances. Similarly, 2a and 3a exhibit a single broadened peak at –74.73 ppm in the ¹⁹F NMR spectra. Analogous coalescence of 2a and 3a has been observed in EtOAc at temperatures higher than 20 °C (cf. Figure 5). When >2 equiv. of DMSO are present, however, this peak appears at –74.81 ppm and is considerably sharpened, consistent with complete conversion of 2a into 3a (and 3b). Complexes 2a and 3a do not interconvert rapidly with 3b at –60 °C; however, when the spectra were recorded at room temperature, fast exchange was observed among all three species (2a, 3a and 3b; Figure S13).

The broad peak corresponding to 2a and 3a exhibits a chemical shift that depends on the relative concentrations of 2a and 3a. We reasoned that with 0.5 equiv. of DMSO, when 3a has not yet started to form, the peak at 3.29 ppm in the ¹H NMR spectrum and –74.73 ppm in the ¹⁹F NMR spectrum arise solely from 2a. With 4 equiv. DMSO, when 2a is consumed, the peaks at 3.26 ppm in the ¹H NMR spectrum and –74.81 ppm in the ¹⁹F NMR spectrum solely represent 3a. The concentrations of 2a and 3a can be calculated on the basis of the chemical shift of the merged peaks, and the concentrations of all of the individual species are plotted as a function of added DMSO in Figure 11. In the presence of ≥ 2 equiv. of DMSO at –60 °C, and equilibrium mixture of the two bis-DMSO coordinated Pd^II complexes, 3a and 3b, is present in very similar concentrations.

Figure 11.

Titration curve of DMSO into the solution of Pd(TFA)₂ in THF-d₈. (A) Pd species derived from ¹H NMR spectra; (B) Pd species derived from ¹⁹F NMR spectra. Conditions: [Pd(TFA)₂] = 15 mM (3.3 mg, 0.01 mmol), THF-d₈ = 0.65 mL, –60 °C, [DMSO] = 0, 7.5, 15, 19.5, 24, 30 and 60 mM.

Comparison of the Kinetics of DMSO Ligand Exchange in EtOAc and THF-d₈

The interconversion between 2a and 3a (eq 8) resulted in line broadening of the separated peaks in EtOAc and coalescence of the peaks in THF-d₈. The rate of this process can be estimated by the peak width at half height, when the intensities of both peaks are equal.²⁹ At –60 °C, the concentrations of 2a and 3a are approximately equal when 1.3 and 1.4 equiv. of DMSO are present in EtOAc and THF-d₈, respectively. The exchange rates are calculated to be 3.3 sec⁻¹ and 116 sec⁻¹, in EtOAc and THF-d₈, respectively, based on the ¹⁹F NMR spectra under these conditions.³⁰ These results, showing that ligand exchange in THF-d₈ is substantially faster than in EtOAc, can be rationalized by a solvent-catalyzed ligand exchange mechanism, in which the better coordination ability of THF³¹ relative to EtOAc leads to faster exchange.³²

The exchange between bound and unbound DMSO was analyzed by 1D NOESY saturationtransfer experiments, commonly called 1D EXSY (Exchange Spectroscopy).³³ When 3 equiv. of DMSO are added to Pd(TFA)₂ in EtOAc or THF-d₈, the solutions contain a mixture of 3a, 3b and unbound DMSO. The EXSY experiments performed on these solution at –60 °C reveal that saturation of the signal of 3b does not affect other peaks. In contrast, excitation of 3a causes inversion of the signal for the unbound DMSO (Figures S14 and S15).³⁴ The lack of saturation transfer of 3b to other species indicates that the DMSO ligands on 3b are not exchanging with the unbound DMSO on the time scale of this experiment (eq 12). In contrast, the saturation transfer from 3a to the unbound DMSO suggests that the DMSO ligand on 3a undergoes fast exchange with the unbound DMSO (eq 13). These results have shown that the O-bound DMSO ligands are kinetically more labile than S-bound DMSO ligands. The exchange of both O- and S-bound DMSO ligands with free DMSO has been previously observed in a solution of [Pd(bpy)(DMSO)Cl][PF₆] in CD₃NO₂ at 35 °C.¹²

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Solution Structures of Pd(TFA)₂/DMSO in AcOH-d₄ and Toluene-d₈

Pd-catalyzed aerobic oxidation reactions with Pd(TFA)₂/DMSO catalyst systems have also been carried out in AcOH and toluene (eqs 1 and 4); however, NMR spectroscopic analyses of mixtures of Pd(TFA)₂ and DMSO suggest that DMSO coordination to Pd^II is not as favorable in these solvents as in EtOAc and THF (Figure 12). Upon addition of 1 equiv. of DMSO to Pd(TFA)₂ in AcOH-d₄, unbound DMSO (2.77 ppm) is the major DMSO species, evident in the ¹H NMR spectrum. Smaller broad peaks present at 3.27–3.56 ppm suggest the presence of a mixture of minor S-bound DMSO-ligated Pd^II species (cf. Table 1). ¹⁹F NMR spectra obtained from the titration experiments similarly exhibit a mixture of different species (Figure S17). Integration of the bound DMSO peaks approaches a 1:1 DMSO:Pd stoichiometry, but only after addition 20 equiv. of DMSO (Figure 13). Possible structures consistent with a 1:1 DMSO:Pd stoichiometry include the monomeric and dimeric species 2a and 2b (see above). The high freezing point of AcOH-d₄ limits the utility of variable-temperature studies to gain further insights into this system.

Figure 12.

¹H NMR spectra of Pd(TFA)₂ in AcOH-d₄ with various quantities of DMSO at 24 °C. Conditions: [Pd(TFA)₂] = 15 mM (3.3 mg, 0.01 mmol), AcOH-d₄ = 0.65 mL, 24 °C, [DMSO] = 0, 15, 30, 90, 300 and 600 mM.

Figure 13.

Titration curves of DMSO into the solution of Pd(TFA)₂ in AcOH-d₄ at 24 °C. Conditions: [Pd(TFA)₂] = 15 mM (3.3 mg, 0.01 mmol), AcOH-d₄ = 0.65 mL, 24 °C, [DMSO] = 0, 15, 30, 90, 300 and 600 mM.

Pd(TFA)₂ does not dissolve readily in toluene-d₈. Addition of 2 equiv. of DMSO to the suspension of Pd(TFA)₂ in toluene-d₈ leads to a bright yellow solution but does not fully dissolve Pd(TFA)₂. These observations indicate that DMSO coordinates to Pd(TFA)₂; however, a ¹H NMR spectrum of this suspension reveals a broad resonance in the region of free DMSO as the major species. A mixture of broad DMSO peaks approximately 0.6 ppm downfield of free DMSO supports the presence of S-bound DMSO ligands coordinated to Pd^II. Further characterization of this system was not pursued because of complications associated with the heterogeneity of this system.

Coordination of the Bidentate Sulfoxide 1,2-Bis(phenylsulfinyl)ethane to Pd(OAc)₂ and Pd(TFA)₂

Recent studies by White and coworkers have highlighted the utility of bidentatesulfoxide ligands in Pd(OAc)₂-catalyzed oxidation reactions, such as allylic acetoxylation.^6c,f,g In light of these results, we briefly investigated the coordination of 1,2-bis(phenylsulfinyl)ethane to Pd(OAc)₂ and Pd(TFA)₂ in EtOAc by ¹H NMR spectroscopy. The ¹H resonances for the phenyl group of the free 1,2-bis(phenylsulfinyl)ethane ligand appear as multiplets between 7.73-7.57 ppm (Figure 14). These resonances are essentially unperturbed upon addition of one equivalent of Pd(OAc)₂ to the solution of ligand. In contrast, substantial changes are evident when Pd(TFA)₂ is combined with the ligand (1:1 ratio) in EtOAc. FTIR spectra were acquired for both Pd-ligand samples upon removing the EtOAc solvent under vacuum. The IR spectra of 1,2-bis(phenylsulfinyl)ethane and of a 1:1 Pd(OAc)₂/1,2-bis(phenylsulfinyl)ethane mixture exhibit strong absorption bands at 1035 cm⁻¹, corresponding to the S–O stretching frequency (Figures S3 and S4). These observations indicate that 1,2-bis(phenylsulfinyl)ethane does not coordinate to Pd(OAc)₂ in EtOAc (eq 14), and this conclusion is consistent with previous studies in dichoromethane and chloroform performed by White and coworkers.^6g In contrast, the 1:1 Pd(TFA)₂/1,2-bis(phenylsulfinyl)ethane mixture exhibits absorption bands at 1182 and 1148 cm⁻¹ Figure S5). These blue-shifted bands are consistent with S-bound sulfoxide ligation.³⁵ No significant absorption bands are observed in the region corresponding to O-bound sulfoxides (1100–800 cm⁻¹). These IR data, together with the ¹H NMR data, show that coordination of 1,2-bis(phenylsulfinyl)ethane to Pd(TFA)₂ is quite favorable (eq 15).

(14)

(15)

Figure 14.

¹H NMR spectroscopic analysis of the mixture of 1,2-bis(phenylsulfinyl)ethane and Pd(TFA)₂ and Pd(OAc)₂ by. Conditions: [1,2-bis(phenylsulfinyl)ethane] = 15 mM (2.7 mg, 0.01 mmol), EtOAc = 0.65 mL, 24 °C, ([Pd(OAc)₂] = 15 mM), ([Pd(TFA)₂] = 15 mM).

Summary and Analysis

The coordination chemistry of the Pd(TFA)₂/DMSO catalyst system in various solvents highlights the complexity of DMSO coordination to Pd^II and subtle, but potentially important, difference between the linkage-isomer coordination modes of DMSO in solution relative to the solid state. The solid-state structure of trans-Pd(DMSO)₂(TFA)₂ exhibits one S- and one O-bound DMSO ligand, whereas our solution-state studies suggest that the structure with two S-bound DMSO ligands is nearly isoenergetic in EtOAc and THF (cf. Figures 6 and 13). When only 1 equiv. of DMSO is present, both the crystallographic and solution-phase spectroscopic data show that DMSO coordinates to Pd^II via the sulfur atom.

The solvent identity has a significant impact on the Pd(TFA)₂/DMSO coordination chemistry. In Scheme 2, the major Pd^II complexes formed in the presence of 2 equiv. of DMSO in different solvents are highlighted in boxes. In EtOAc and THF-d₈, DMSO coordination to Pd affords an equilibrium mixture of monomeric Pd(DMSO)₂(TFA)₂ linkage isomers. DMSO coordinates less effectively to Pd(OAc)₂, relative to Pd(TFA)₂, and also less effectively to Pd(TFA)₂ in AcOH and toluene, relative to EtOAc and THF-d₈. In these cases, the substoichiometric coordination of DMSO to Pd^II is evident from the spectroscopic data, probably reflecting the presence of bi- or trinuclear Pd^II-carboxylate species that are not fully cleaved by DMSO.

Scheme 2.

Summary of Solution Structures of Pd(TFA)₂/DMSO in Various Solvents

O-Bound DMSO ligands are considerably more labile than S-bound DMSO in Pd(TFA)₂/DMSO complexes. It seems reasonable that O- and S-bound DMSO ligands may work cooperatively in successful catalytic reactions. For example, a labile O-DMSO ligand might be important to enable weakly coordinating L-type ligands such as carbonyl oxygen atoms, alkenes, sulfonamide nitrogen atoms, and arene C–H bonds (cf. eqs 1–4) to access the coordination sphere of Pd^II. This insight might explain the lack of catalytic activity exhibited by Pd(TFA)₂ coordinated with a bidentate bis(phenylsulfinyl)ethane ligand in dehydrogenation and oxidative amination.^7,8 This ligand chelates to Pd^II via the sulfur atom of the two sulfoxides.^{Error! Bookmark not defined.} On the other hand, the more-strongly-coordinating S-DMSO ligand might be important in other steps of the catalytic mechanism. For example, the present studies do not address DMSO coordination to Pd⁰; however, the "softer" character of Pd⁰ relative to Pd^II suggests that DMSO will coordinate to Pd⁰ preferentially via the sulfur atom.⁵ Such coordination of DMSO to Pd⁰ should stabilize the Pd⁰ intermediate by inhibiting its aggregation into Pd black and facilitating oxidation of the catalyst by O₂.We speculate that the beneficial effect of DMSO in catalytic reactions carried out in AcOH and toluene might reflect this interaction of DMSO with Pd⁰, espite the poor coordinating ability of DMSO to Pd^II in these solvents.

Experimental

All commercially available compounds were ordered from Sigma-Aldrich except for Pd(TFA)₂, which was obtained from Strem. EtOAc was purified by fractional distillation under N₂. All samples were prepared and experiments carried out in air.

¹H and ¹⁹F NMR spectra were acquired on a Varian INOVA-500 MHz spectrometer. The chemical shifts (δ) of ¹H NMR spectra are given in parts per million and referenced to solvent, non-deuterated CH₃CO₂Et (2.05 ppm) and the residual C3/C4 ethylene protons of THF-d₈ (1.73 ppm). The chemical shifts (δ) in the ¹⁹F NMR spectra were referenced relative to the corresponding ¹H spectra. Spectra were processed with MestReNova™ software. Infrared spectra were obtained with a Bruker Tensor 27 spectrometer equipped with a single reflection MIRacle Horizontal ATR ZnSe crystal by Pike Technologies.

Preparation of Pd(S-DMSO)(O-DMSO)(TFA)₂

Crystals of Pd(S-DMSO)(O-DMSO)(TFA)₂ were obtained by vapor diffusion of hexane into an EtOAc solution of Pd(TFA)₂ and 2 equiv. of DMSO at room temperature. Pd(TFA)₂ (8.4 mg, 0.25 mmol) was dissolved in 0.5 mL of EtOAc, forming a deep red solution. The solution turned bright yellow upon addition of DMSO (3.6 μL, 0.5 mmol). This solution was filtered through glass wool into a 4 mL vial and then transferred into a 15 mL vial containing 4 mL hexane. The vial was sealed with a Teflon cap and maintained at room temperature overnight. Deep orange crystalline needles formed.

Preparation of the Pd(S-DMSO)(OH₂)(TFA)₂ Complex

Crystalline Pd(S-DMSO)(OH₂)(TFA)₂ was obtained by vapor diffusion of pentane into an EtOAc solution of Pd(TFA)₂ and 1 equiv. of DMSO at low temperature. Pd(TFA)₂ (8.4 mg, 0.25 mmol) was dissolved in 0.5 mL of EtOAc to form a deep red solution. Upon addition of DMSO (1.8 μL, 0.25 mmol), the solution turned bright yellow. The solution was filtered through glass wool into a 4 mL vial, and then transferred into a 15 mL vial containing 4 mL pentane. The vial was sealed with a Teflon cap and placed in refrigerator at –15 °C. After 4 days, orange crystalline needles formed.

NMR Spectroscopic Study of Pd(TFA)₂/DMSO in EtOAc

Pd(TFA)₂ (6.6 mg, 0.02 mmol) was weighed into a vial, followed by injection of EtOAc (0.64 mL). The suspension transformed into a deep red solution upon sonicating for 10 min. Fluorobenzene (4 μL, 0.041 mmol) was injected as an internal standard. The solution was transferred into an NMR tube. The spectrometer probe was pre-cooled to the desired temperature and allowed to equilibrate for 30 minutes. The sample was unlocked and the ¹H channel was used to perform gradient shimming. A ¹H NMR spectrum was acquired followed by tuning the probe for ¹⁹F and acquiring a ¹⁹F NMR spectrum. Additional quantities of DMSO were then added from a stock solution into the same sample. The sample was allowed to mix at room temperature for 5 min, cooled to the desired temperature, and the spectrum was recorded. Longer mixing time was tested and resulted in no change of the spectrum. The volume change caused by titration was controlled to be less than 5% over the course of the experiments.

NMR Spectroscopy Study of Pd(TFA)₂/DMSO in THF-d₈

Pd(TFA)₂ (3.3 mg, 0.01 mmol) was weighed into a vial. THF-d₈ (0.64 mL) was injected to form a deep red solution and then fluorobenzene (4 μL, 0.041 mmol) was added as an internal standard. The solution was transferred into an NMR tube. The spectrometer probe was pre-cooled to the desired temperature and allowed to equilibrate for 30 minutes. A ¹H NMR spectrum was acquired followed by tuning the probe for ¹⁹F and acquiring a ¹⁹F NMR spectrum. Additional quantities of DMSO were then added from a stock solution into the same sample. The volume change caused by titration was controlled to be less than 5% over the course of the experiments.

This procedure was also used for the NMR Spectroscopy studies of Pd(TFA)₂/DMSO in AcOH-d₄ and Pd(OAc)₂/DMSO in EtOAc.

NMR Spectroscopy Study of Pd(TFA)₂/DMSO in toluene-d₈

Pd(TFA)₂ (3.3 mg, 0.01 mmol) was weighed out in a vial and formed a suspension with addition of toluene-d₈ (0.64 mL). Pd(TFA)₂ dissolved to afford a yellow solution upon addition of 2 equiv. of DMSO. Fluorobenzene (4 μL, 0.041 mmol) was injected as the internal standard. The NMR spectra were acquired the same way as described above.