# Unravelling the mechanism for the mono-alkoxycarbonylation of butadiene: what is the role of the base?

Mohammad Ameskal, Lionel Magna, Juan M Asensio, Pascal Raybaud

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Mohammad Ameskal, Lionel Magna, Juan M Asensio, Pascal Raybaud. Unravelling the mechanism for the mono-alkoxycarbonylation of butadiene: what is the role of the base?. Journal of Catalysis, 2025, 450, pp.116235. 10.1016/j.jcat.2025.116235. hal-05154686

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Research article

# Unravelling the mechanism for the mono-alkoxycarbonylation of butadiene: what is the role of the base?

Mohammad Ameskal, Lionel Magna, Juan M. Asensio*, Pascal Raybaud*

IFP Energies Nouvelles, Rond-point de l'échangeur de Solaize. BP3, 69360 Solaize, France

## ARTICLE INFO

### Keywords:

Alkoxycarbonylation

Palladium

Mechanism

DFT

Butadiene

## ABSTRACT

The mechanism of catalytic alkoxycarbonylation of alkenes has been extensively studied and it is generally accepted that it elapses through three elementary steps: (i) alkene insertion into a Pd—H bond, (ii) carbonylation, and (iii) alkooholysis. In the case of butadiene methoxycarbonylation catalyzed by [Pd(d'bpx)H]⁺, we have identified the formation of a highly stable Pd(η³-allyl) intermediate by Density Functional Theory (DFT) calculations and Nuclear Magnetic Resonance (NMR). This intermediate makes the apparent kinetic barrier of the mechanism incompatible with experimental observations (ca. 200 kJ·mol⁻¹). Upon coupling DFT calculations and experimental analysis, we proposed a revised mechanism founded on a "base assisted" pathway where the mono-alkoxycarbonylation of dienes exhibits a significantly decreased free energy of activation (ca. 100 kJ·mol⁻¹). Hence, we proposed that the base coming from the Pd precursor is non-innocent and participates in the reaction upon acting as proton shuttle during the alkoholysis step. By considering various acid/base pairs, we further refined these findings and demonstrated that an optimum balance between the acid and the base must be found, regarding strengths and concentrations, to maximize the catalytic activity.

## 1. Introduction

Catalytic alkoxycarbonylation with carbon monoxide (CO) and an alcohol is a highly desirable method for producing esters from olefins due to its high atom-economy [1–3]. Among various catalytic systems, palladium-based catalysts have earned significant attention due to their high activity under relatively mild conditions, outperforming other metals like iron (Fe), cobalt (Co), ruthenium (Ru), rhodium (Rh), iridium (Ir), platinum (Pt), and molybdenum (Mo) [4,5]. This reaction has been extensively studied for highly available substrates such as ethylene [6–8] or fatty acids [9,10]. More recently, some works have focused on the alkoxycarbonylation of butadiene (BD) [11,12]. This process leads to the formation of pentenoates (MPs), which serve as key intermediates in the large-scale production of essential monomers like ε-caprolactam [13–15].

More interestingly, the double alkoxycarbonylation of butadiene may enable to produce adipate esters in a single step. These C₆ building blocks are essential monomers for industrial processes such as Nylon-6,6 synthesis [14]. Currently, adipic acid is produced from cyclohexane, a

petrochemical resource, in a process that is energy demanding and produces important amounts of N₂O which is a greenhouse gas [16]. Hence, there is a need to find alternative synthetic routes starting from potentially renewable sources like butadiene, which can be prepared from bioethanol [17], and CO, which could be obtained from CO₂ through the reverse water–gas shift reaction [18].

The first one-pot alkoxycarbonylation of butadiene to selectively obtain the linear adipate ester was reported by Yang et al. [14]. The Pd (TFA)₂/HeMaRaphos system demonstrated good activity and selectivity when the reaction was carried out in neat alcohol (nBuOH) acting as both solvent and reagent (see Scheme 1, a). The same group extended this methodology by combining Pd(TFA)₂ with the commercially available 1,2-bis((di-tert-butylphosphino)methyl)benzene (d'bpx) ligand, achieving excellent selectivity in butadiene methoxycarbonylation in toluene [15]. This was accomplished using p-toluenesulfonic acid monohydrate (p-TsOH·H₂O) as a co-catalyst under 40 bar of CO at 120 °C, in the presence of 4 equivalents of methanol (Scheme 1, b).

The catalytic cycle proposed by the authors followed the well-

**Abbreviations:** Pd (TFA)₂, palladium (II) trifluoroacetate; Pd(OAc)₂, palladium (II) acetate; p-TsOH·H₂O, p-toluenesulfonic acid monohydrate; p-TsO⁻, p-toluenesulfonate; NaOAc, sodium acetate; OAc⁻, acetate; NaTFA, sodium trifluoroacetate; TFA⁻, trifluoroacetate and d'bpx, 1,2-Bis(di-tert-butylphosphinomethyl)benzene.

<footnote>* Corresponding authors.</footnote>

<footnote>E-mail addresses: juan-manuel.asensio-revert@ifpen.fr (J.M. Asensio), pascal.raybaud@ifpen.fr (P. Raybaud).</footnote>
established Pd-hydride pathway (Fig. 1) [6,19,20]. It initiates with co-ordination of BD followed by the insertion of the double bond into the Pd—H, generating the Pd($\eta^3$-allyl)complex (step 1). After CO coordination and insertion (step 2), methanolysis leads to methyl pent-3-enoate (3MP) regenerating the active species (step 3). Step 3 is thus suspected to occur via a concerted mechanism, involving the formation of the (O)C-O (ester) and Pd—H bonds, along with the cleavage of the O—H (alcohol) and Pd-CO bonds. To yield the required dimethyl adipate (dma), this monoester should be subjected to olefin isomerization, presumably leading to methyl pent-4-enoate (4MP), which is then incorporated into the second alkoxycarbonylation cycle (steps 1'-3').

While several density functional theory (DFT) studies have identified

the rate-determining step (rds) in the case of simpler olefins and fatty acids [2,8,9], a recent investigation by Yu et al. represents the first detailed analysis for butadiene (BD) [22]. This DFT study (undertaken in absence of a solvation model) identified methanolysis as the rds in both alkoxycarbonylation cycles, proceeding through a concerted mechanism. While this work has provided valuable insights, there remain opportunities for further exploration. In particular, the role of solvent should be analyzed more properly, and one must note that the possible formation of a Pd($\eta^3$-allyl) complex, a key intermediate after BD insertion into the Pd—H bond, which was not considered by the authors, may impact the overall activation free energy.

Additionally, to consider the explicit effect of methanol molecules in

<figure><img src="image_3.png" /><figcaption>**Scheme 1.** Butadiene alkoxycarbonylation: a) in the presence of HeMaRaphos [14], b) in the presence of $d^t$bpx [15], c) in the presence of Xantphos [24], d) the impact of external base additives on alkoxycarbonylation according to Han et al. [24] e) the impact of a ligand built-in base on alkoxycarbonylation according to Yang et al. [21].</figcaption></figure>
<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Proposed catalytic cycles for the Pd-catalyzed double methoxycarbonylation of BD.</figcaption></figure>

the surrounding of the catalytic active site, DFT calculations have explored the impact of the formation of a two or three methanol/water molecules cluster during solvolysis, in the case of simpler alkenes [8,9,21,23]. This cooperative effect of the solvent molecules seems generally to decrease the activation energy, although it is not recovered in all cases [21].

Moreover, some works have also considered the involvement of a base in the mechanism, which can be external (Scheme 1, d) [24], or as a part of the ligand structure (Scheme 1, e) [21]. Thus, the high activities obtained by HeMaRaphos ligand have been explained by participation of the pyridine moiety into the reaction mechanism upon accepting the proton from MeOH generating a Pd(0) complex containing a pyridinium group (Scheme 1, e). This pyridinium can protonate the alkene substrate to generate the corresponding Pd(II)-alkyl that starts a new catalytic cycle. Analogously, Han et al. explored this “base-assisted” pathway by examining the impact of external pyridine derivatives on the Pd(cod) Cl₂/Xantphos-catalyzed methoxycarbonylation of BD to methyl pent-3-enoate (3MP) (Scheme 1, d) [24]. They demonstrated that pyridine derivatives facilitate methanol deprotonation during methanolysis. However, although the “base-assisted” mechanism has been already

suggested in the literature [21], it is usually neglected in most of the mechanistic studies. We thus plan to revisit it more cautiously in this work.

Herein, we aim to deepen the understanding of the butadiene monoalkoxycarbonylation reaction pathway. We first revisit, using DFT calculations, the reaction mechanism starting from the mono-cationic Pd (1,2-bis-ditert-butylphosphinomethylbenzene)hydride complex. Due to the high stability of the Pd(η³-allyl) intermediate we will show how the methanolysis step exhibits a considerably high barrier, which is incompatible with reaction conditions using toluene as solvent. To overcome this, we will explore the non-innocent role of the base considering that the Pd precursor contains 2 equivalents of base in its structure, namely acetate (OAc⁻) or trifluoroacetate (TFA⁻).

To further bridge our theoretical findings with experimental evidence, we will conduct a two-dimensional experimental study examining how variations in acid-to-base ratios impact the efficiency of the catalytic mono-alkoxycarbonylation of butadiene to methyl pent-3-enoate (3MP). For that purpose, our study will employ two relevant acid-base pairs: p-toluenesulfonic acid (p-TsOH) with either NaOAc or NaTFA. This will allow us to identify the optimal acid-base ratio for each catalyst precursor.

## 2. Results and discussion

### 2.1. Methoxycarbonylation mechanism starting from palladium-hydride

The catalytic cycle for butadiene alkoxycarbonylation by Pd/d¹bpx/p-TsOH was modeled at the DFT level (according to the approximations provided in the Experimental Section). It is inspired by the commonly accepted mechanism, which involves a palladium-hydride complex as the active species [20]. As a preliminary step, we explored potential complexations of the Pd-hydride complexes with BD, methanol, or carbon monoxide (Fig. S1 in the SI). Assuming the same concentration and partial pressure for all reactants, the results reveal that the CO-bound complex (H-CO) is notably more stable than other species. Hence, H-CO was selected as the resting state and thus the reference point for the energies. The Gibbs free energy (ΔG) and enthalpy (ΔH) profiles for the Pd-catalyzed mono-methoxycarbonylation of BD starting from H-CO leading to the formation of the monoester 3MP are depicted in Fig. 2.

Following the endergonic CO exchange by BD, the initial step involves the 1,1-insertion of the C₁-C₂ double bond into the Pd-H bond of complex A. This reaction is exergonic, as the resulting Pd(η³-allyl) complex (B) is 96 kJ·mol⁻¹ more stable than A (Fig. S2 in the SI). Furthermore, the transition state TS<sub>A-B</sub> exhibits a low energy barrier of 33 kJ·mol⁻¹ relative to H-CO, indicating that the alkene insertion-β-hydride elimination equilibrium is fast but irreversible at room temperature, favored towards the formation of complex B.

Upon the formation of B, the subsequent CO coordination is found to be endergonic with a ΔG of 80 kJ·mol⁻¹, leading to intermediate C, which then proceeds through CO insertion via the transition state TS<sub>C-D</sub>, featuring an energy barrier of 100 kJ·mol⁻¹ relative to B. This relatively high barrier is due to the entropic contribution given for the coordination-insertion of toluene-solvated CO. The resulting Pd-acyl complex D is 30 kJ·mol⁻¹ more stable in comparison to C, which can be explained by the interaction between the oxygen atom of the acyl group and the palladium center in a partial η² coordination [9]. At this stage, the subsequent CO uptake by D is endergonic by 20 kJ·mol⁻¹ (Fig. S3 in the SI).

Finally, the complex D undergoes endergonic methanol coordination leading to complex E, followed by methanolysis, which finalizes the catalytic cycle and produces the monoester 3MP. By applying the energetic span model [25] and identifying intermediate B as the TOF-determining intermediate (TDI) and TS<sub>E-3MP</sub> as the TOF-determining transition state (TDTS), the highest Gibbs free energy barrier (ΔG‡) for the mono methoxycarbonylation of BD, specifically associated with methanolysis, is 202 kJ·mol⁻¹. The value previously reported by Yu
<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Gibbs free energy profile of the Palladium (II)-catalyzed methoxycarbonylation of 1,3-butadiene into **3MP**, following the hydride mechanism at 298.15 K and 1 atm. ωB97XD/TZVP(C,H,P,O)/LANL2DZ(Pd)/CPCM (toluene) was used as level of theory (P*P = d*bpx).</figcaption></figure>

et al. was 123 kJ·mol⁻¹ [22]. This discrepancy arises from their omission of the Pd(η³-allyl) pathway, whose stability significantly raises the energy cost. Indeed, by considering our B'' σ-allyl complex (Fig. S2) only, the activation free energy would be decreased by 79 kJ·mol⁻¹ since the new TDI becomes the starting complex **H-CO**.

Within the transition state (TS<sub>E→3MP</sub>), the methanol molecule reorients to enable O—H bond activation. Here, methanol rotates such that its O—H bond faces the palladium center, with the hydrogen atom positioned closer to palladium (Fig. 3). As the O—H bond is cleaved, the proton transfers to the palladium, generating a palladium hydride species. Additionally, the acyl group shifts slightly away from the palladium, allowing C—O coupling as can be deduced from the shortening of the distance between the two atoms from 2.59 Å in E to 1.67 Å in **TS<sub>E→3MP</sub>**. We also noticed a weak elongation of the MeO-H bond from 0.96 Å in E to 1.00 Å in **TS<sub>E→3MP</sub>**, evidencing that O—H cleavage is challenging and very likely is the driving force for this elementary step.

As above mentioned, it was also proposed in the literature that modelling the concerted methanolysis by using a cluster of 2 or 3 methanol molecules surrounding the Pd complex can mimic the effect of methanol solvation [8,9,23]. However, the different putative steps of this approach do not follow a general rule, and they are often seen as a single elementary step. Given this consideration, we decided to revisit this approach in our investigation. The resulting Gibbs free energy profile is presented Fig. S4 (see section SI 1.5 for a more detailed discussion). According to our calculations, using a three-molecule cluster for the first methanolysis reduces the corresponding apparent activation free energy to 160 kJ·mol⁻¹, which is well aligned with literature [8,9,23]. Although we confirm earlier results showing a non-negligible decrease of this apparent activation energy, it is important to note that this value remains significantly high [24].

Even by considering the uncertainties of DFT calculated values, it is clear that these high apparent energy barrier (above 160 kJ·mol⁻¹) in the methoxycarbonylation of BD appears to be incompatible with the experimental knowledge showing that the first methoxycarbonylation cycle is accessible at 100 °C (see below) [15]. Hence, the proposed mechanisms may be questionable. It is thus the purpose of the next section to investigate an alternative mechanism.

## 2.2. Alternative mechanisms: base assisted alcoholysis

At this stage, we propose to consider a base-assisted mechanistic

<figure><img src="image_6.png" /><figcaption>**Fig. 3.** Analysis of the most relevant bond distances during methanol coordination (E) and methanolysis (TS<sub>E→3MP</sub>).</figcaption></figure>
pathway motivated by the fact that the catalytic system contains different putative bases, namely, *para*-toluenesulfonate (p-TsO⁻) as the conjugated base of p-TsOH, acetate (OAc⁻) with its conjugated acid (HOAc) and trifluoroacetate (TFA⁻) with its conjugated acid (TFAH). These bases can be generated in the medium from the Pd precursors, Pd (OAc)₂ and Pd(TFA)₂, which will also be explored experimentally (see below).

Following this scenario, we deconstructed the base-assisted pathway into three additional elementary steps (4 to 6 in Fig. 4, while steps 1, 2, and 3 remain BD insertion, carbonylation and methanol coordination as depicted in Fig. 1 and are omitted for clarity): (4) the interaction of the methanol present in complex E with the base, resulting in the formation of the corresponding base-methanol adduct. This step was evaluated by reaction thermodynamics (ΔG<sub>E→K</sub>). (5) Base-assisted reductive elimination yielding the monoester 3MP alongside the resting state L after CO coordination to Pd(0). We assessed both the thermodynamics and kinetics by identifying the transition state for this step (TS<sub>K→L</sub>) and the corresponding activation barriers (ΔG̸<sub>K→L</sub>). (6) Oxidative re-protonation of palladium (0) by the conjugated acid, which we also evaluated based on reaction thermodynamics (ΔG<sub>L→3MP</sub>). This reaction pathway was examined for the three potential base/acid couples that can participate in the reaction: p-TsO⁻/p-TsOH, OAc⁻/HOAc and TFA⁻/TFAH.

Calculations using pure toluene solvent failed to accurately reproduce the observed reaction rates (see Table S4 and Fig. S5 in section SI 1.6.1 for a detailed discussion). While the base effectively accelerated the methanolysis step, a new *rds* emerged: the oxidative Pd(0) re-protonation. This step exhibited a too high energy barrier to be overcome under experimental conditions. Moreover, cationic Pd complexes

remain soluble in toluene as observed experimentally (for example, cationic complex B is highly soluble in toluene, see below), the polar additives used (such as p-TsO⁻, TFA⁻, or OAc⁻) demonstrated very limited solubility, even at elevated temperatures.

An alternative approach involved considering pure methanol as a solvent to establish a solvation regime that stabilizes polar intermediates (Fig. S6 and Table S5 in section SI 1.6.2). Experimentally, previously insoluble additives like p-TsO⁻, TFA⁻, and OAc⁻ readily dissolved in the reaction mixture just after addition of MeOH. However, computational results show that, under these methanol-solvated conditions, the *rds* was the reductive elimination (4), with reduced energy barriers relative to those in pure toluene. However, the apparent kinetic barriers were considerably higher, given the stability of the Pd(η³-allyl) intermediate B, which acts as TDI. It has been reported that this reaction is not feasible in neat MeOH [15]. Whereas this could be linked to the higher barrier found in our DFT study, one must consider this fact may also be related to the instability of palladium hydride species, which can lead to hydrogen evolution and catalyst deactivation, preventing the catalytic cycle from proceeding [26–29].

Hence, we propose a third solvation approach mimicking the experimental observations. Following this scheme, we applied a two-solvent approach considering toluene as the solvent for the metallic complexes and methanol for the acids and bases. While we are aware that applying a more rigorous approach considering explicit molecules would be a better reflect of the actual micro-solvation environment, this simplified approach should be seen as a reasonable compromise for the present work in order to reflect the experimental conditions more closely, capturing both the stabilizing effects of toluene on intermediates and the critical role of methanol in facilitating acid-base interactions. Gibbs free energy calculations for key steps are summarized in Table 1, while the different pathways are displayed in Fig. 5.

The interaction between the bases and complex E to yield K is exergonic for the three cases, with the acetate adduct being the most stable since this molecule is the strongest base among the three candidates. For each base, we successfully identified the concerted transition state (TS<sub>K→L</sub>) where the base participates in the cleavage of the O—H bond of methanol, allowing the methoxy and acyl groups to couple and form the monoester 3MP.

The apparent energy barriers calculated for methanolysis (B à TS<sub>K→L</sub>) show that p-TsO⁻ has an intrinsic activation barrier of 115 kJ·mol⁻¹, TFA⁻ is slightly lower at 98 kJ·mol⁻¹, and acetate presents the lowest barrier at 53 kJ·mol⁻¹.

Taking OAc⁻ as an example, the transition state (TS<sub>K→L</sub>) reveals that methanol rotates such that its O—H bond is oriented toward the OAc⁻, positioning the hydrogen atom closer to the oxygen of OAc⁻ (Fig. 6). A marked elongation of the MeO—H bond, increasing from 1.04 Å in K to 1.57 Å in TS<sub>K→L</sub>, provides evidence of an easier MeO—H cleavage and a formation of the AcO—H bond, which shortens from 1.46 Å in K to 1.01 Å in TS<sub>K→L</sub>. Furthermore, the acyl group undergoes a slight shift away from palladium, facilitating C—O coupling, as indicated by the reduction of this distance from 2.63 Å in K to 1.87 Å in TS<sub>K→L</sub>. As discussed in section SI 1.6.4, the evolution of the MeO-H bond distance in TS<sub>K→L</sub> for the different bases used, underlines that the cleavage of this bond is the driving force of the methanolysis step.

Following methanolysis, the Pd(0) complex (L) together with the conjugated acid are generated with rather strong exergonicity depending on the nature of the base.

Finally, the oxidative re-protonation of the complex (L + B-H → H-CO + B⁻) occurs thanks to the conjugate acid. This step is endergonic with an energy balance depending on the acid: 55 kJ·mol⁻¹ for p-TsOH, 68 kJ·mol⁻¹ for TFAH, and 143 kJ·mol⁻¹ for HOAc.

According to the energetic span concept [25], the Pd(η³-allyl) complex B remains the TDI for p-TsO⁻/p-TsOH and TFA⁻/TFAH. However, for OAc⁻, intermediate L becomes the TDI. TDTs is either TS<sub>K→L</sub> for or p-TsO⁻/p-TsOH and TFA⁻/TFAH, or TS<sub>C→D</sub> for OAc⁻. Therefore, the apparent activation energy varies depending on the base used. For

<figure><img src="image_7.png" /><figcaption>**Fig. 4.** Base-assisted methanolysis pathway proposed for our DFT investigation.</figcaption></figure>
<caption>**Table 1**</caption>

Gibbs free energy values (kJ·mol⁻¹), considering different solvent models, for the chosen steps in the base-facilitated methanolysis, and resulting apparent kinetic barrier according to energetic span.

<table><thead><tr><th></th><th></th><th>(Step 4)<br>Base-methanol<br>interaction</th><th>(Step 5)<br>Reductive elimination</th><th>(Step 6)<br>Oxidative<br>re-protonation</th><th>Apparent kinetic barrier<br>(TDI → TDTS)</th></tr></thead><tbody><tr><td>Solvent</td><td>(acid-base)</td><td>ΔG<sub>E→K</sub></td><td>ΔG<sup>‡</sup><sub>K→L</sub></td><td>ΔG<sub>L→3MP</sub></td><td>appΔG<sup>‡</sup><sub>TDI→TDTS</sub></td></tr><tr><td rowspan="3">Toluene (Pd complexes)-Methanol (acid-base)</td><td>p-TsOH-p-TsO<sup>−</sup></td><td>−36</td><td>70</td><td>55</td><td>115 (B → TS<sub>K→L</sub>)</td></tr><tr><td>TFAH-TFA<sup>−</sup></td><td>−45</td><td>62</td><td>68</td><td>100 (B → TS<sub>C→D</sub>)</td></tr><tr><td>HOAc-OAc<sup>−</sup></td><td>−68</td><td>40</td><td>143</td><td>174 (L → TS<sub>C→D</sub>)</td></tr></tbody></table>

<figure><img src="image_8.png" /><figcaption>**Fig. 5.** Gibbs free energy profile of the base-assisted methanolysis at 298.15 K and 1 atm, using ωB97XD/TZVP (C, H, P, O)/LANL2DZ(Pd)/CPCM (toluene) for all intermediates and CPCM (methanol) for Base/Base-H. (P:P: d'bpx). For clarity, only relevant intermediates and transition states are represented; step (1): BD insertion; step (2): carbonylation, step (3): methanol coordination; step (4): base-methanol interaction; step (5): base-assisted reductive elimination; step (6): oxidative re-protonation.</figcaption></figure>

acetate, the high energy span (174 kJ·mol⁻¹), is explained by the too strong stabilization of the conjugated HOAc which is liberated in the formation of L. Conversely, for both TFA⁻ and p-TsO⁻, the apparent energies obtained by energetic span concept are 100 and 115 kJ·mol⁻¹ respectively. This significant decrease of the apparent activation energy is due to the less stable states of the acids. As aforementioned, this evolution is intrinsically linked to the pKₐ of respective acids.

This proposed base assisted mechanism clearly reveals a significant decrease of the TDTS (TSₖ⁻L) energy level with respect to the concerted mechanisms, while keeping the same TDI (Pd(η³-allyl) complex B). Therefore, the apparent activation energies (100–115 kJ mol⁻¹ vs 160–200 kJ mol⁻¹) become much more compatible with the experimental feasibility of this reaction. We can thus conclude from our DFT modelling that the already published reaction mechanism of butadiene alkoxycarbonylation must be reconsidered by including a direct involvement of complex B and the base.

Moreover, DFT calculations also show that the strength of the base would have different impact on the reaction. In the present case, the three simulated bases (OAc⁻, TFA⁻, and p-TsO⁻) exhibit the following pKₐ (in water): 9.2, 13.8 and 16, respectively. Hence, the pKₐ value is inversely correlated with the exergonicity of the base-methanol interaction (step 3 in Fig. 5) and with the endergonicity of re-protonation (step 5 in Fig. 5). At the same time, the energy level of the TDTS (TSₖ⁻L) is pushed down which might be seen as a positive effect for the kinetics. Interestingly, the intrinsic activation barrier of the methanolysis (ΔG‡ₖ⁻L) is also directly correlated with the exergonicity of the K → L transformation and thus with the pKₐ value, following a Brønsted-Evans-Polanyi principle. However, in the case of OAc⁻, TDTS and TDI change, as it was explained previously and thus the energetic span increases. As a consequence, an optimal pKₐ (not too high, not too low) is expected to be chosen to minimize the energetic span.

Hence, we proposed some experimental investigations in the following section to confirm our theoretical predictions. For that purpose, we will combine various acid/base couples at different ratios to explore their effect on the reactivity.

## 2.3. Reaction benchmark and insights into the role of the base in butadiene methoxycarbonylation

The main conclusion of our DFT study concerning the role of the base assumes that the high kinetic barrier of methanolysis is partly due to the stable formation of the Pd(η³-allyl) intermediate acting as TDI, while other theoretical studies do not consider this intermediate but σ-allyl instead. As a first step, to confirm this theoretical finding, we contacted BD with 3 mol% of two Pd(II) precursors, namely Pd(OAc)₂ or Pd(TFA)₂, with 6 mol% of d'bpx and 12 mol% of p-TsOH, in the absence of CO during 2 h (Scheme 2). The mixture was characterized by ¹H and ³¹P NMR spectroscopy.

NMR spectroscopy revealed the formation of a palladium allyl complex, [(d'bpx)Pd(η³-C₄H₇)]⁺ in both cases, as the major product (ca. 90 % determined from integration in the ³¹P NMR) as shown in Scheme 2. A by-product at 39.6 ppm was also observed whose nature could not be determined. Notably, this allyl complex persisted as the major species even after extended reaction times, strongly indicating that it represents a thermodynamic stable intermediate, as predicted by our DFT calculations. The characteristic signals observed in NMR spectra were consistent with previously reported data for the same cationic palladium allyl species described by Roesle et al. [9]) (see Figs. S7-S9 in the SI). Indeed, the authors showed that the Pd-allyl complex remained the major species even after exposure to 5 bar of CO [9], without isomerization to the σ-allyl form. Upon increasing the temperature, some alkoxycarbonylation was observed, although no reaction intermediates
<figure><img src="image_9.png" /><figcaption>**Fig. 6.** Analysis of the most relevant bond distances during base-methanol interaction (K) and base-assisted methanolysis (TS<sub>K→L</sub>) where the base is acetate.</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>**Scheme 2.** The formation of [(d'bpx)Pd(η<sup>3</sup>-C<sub>4</sub>H<sub>7</sub>)]<sup>+</sup>, presumably following butadiene insertion into the Pd-hydride bond.</figcaption></figure>

could be detected. Similarly, Beller et al. demonstrated that [(dppb)Pd(η<sup>3</sup>-C<sub>4</sub>H<sub>7</sub>)]<sup>+</sup> was the major reaction product after addition of butadiene to a mixture of Pd<sub>2</sub>(dba)<sub>3</sub>, dppb and HBF<sub>4</sub>, even in the presence of 50 bar of CO, with no detectable formation of a Pd-acyl species even after prolonged CO exposure [30].

As a second step, our goal was to validate experimentally the potential role of the base also predicted by DFT calculations. We first benchmarked our results against experimental conditions reported in the literature, focusing only on the mono-alkoxycarbonylation of butadiene [15]. The reactions were conducted by using toluene as solvent under 30 bar of CO, in the presence of 5.5 equivalents of methanol with respect to butadiene, 3 mol% of Pd(TFA)<sub>2</sub>, 6 mol% of d'bpx and 12 mol% of p-TsOH·H<sub>2</sub>O.

To gain an initial insight and evaluate the influence of temperature,

we conducted the reaction for 2 h at both 100 °C and 120 °C, and then for 24 h at 120 °C. **Table 2** summarizes the results obtained at both temperatures.

As it can be observed, the methoxycarbonylation of butadiene occurred rapidly at 120 °C (93 % conversion of BD), resulting in the formation of 44 % of the monoester (3MP) after two hours. This monoester then underwent isomerization to yield 40 % of the thermodynamic product (2MP), with only 3 % of the terminal monoester (4MP). Additionally, a small amount of the diester, dimethyl adipate was observed (dма, 6 %). After 24 h at 120 °C, approximately 54 % of the monoesters were converted into **dма**.

In contrast, at 100 °C, BD conversion drops considerably, leading only to the kinetic product (3MP) with almost no isomerization to 2MP or 4MP. Minor quantities of butenyl ethers (E1 + E2) were also detected, which can be attributed to the parasite hydromethoxylation of butadiene [31]. This side reaction involves the nucleophilic attack of methoxide on the η<sup>3</sup>-allyl complex, a phenomenon which has been well-documented in previous literature [32,33]. Moreover, the fact that hydromethoxylation takes place suggests that the Pd(η<sup>3</sup>-allyl) intermediate is involved in the catalytic cycle.

From these experiments, we can conclude that the kinetic barrier for the first alkoxycarbonylation should be accessible under our experimental conditions since moderate conversions were obtained after only 2 h at 100 °C. These observations are well aligned with the work of Han and co-workers, in which the catalytic system composed of Pd(COD)Cl<sub>2</sub>/Xantphos afforded 55 % yield to 3MP after 6 h under comparable conditions (40 atm, 120 °C) [24].

One should also note that 3MP is practically the main product of the reaction at 100 °C. However, in some mechanistic studies reported in the literature, 4MP was proposed as reaction outcome [22,34]. This was due to the omission of the Pd(η<sup>3</sup>-allyl) intermediate in the catalytic cycle. If one considers butadiene insertion to give the Pd(σ-but-3-enyl) derivative followed by direct alkoxycarbonylation, the double bond will remain at the terminal position. Since we have confirmed experimentally the formation of intermediate **B**, and 3MP as the kinetic product, we conclude that our experimental findings support our DFT mechanism and raise the importance of considering intermediate **B** for a reliable reaction mechanism.

We then decided to conduct all following reactions at 100 °C to stop at the mono-alkoxycarbonylated product and to avoid being hindered by competing isomerization and **dма** formation. We explored various Pd (II) precursors containing basic ligands displaying different pK<sub>b</sub> values: Pd(OAc)<sub>2</sub> (pK<sub>b</sub> OAc<sup>-</sup> = 9.2), Pd(TFA)<sub>2</sub> (pK<sub>b</sub> TFA<sup>-</sup> = 13.8) and Pd(acac)<sub>2</sub> (pK<sub>b</sub> acac = 5.1). We also tested PdBr<sub>2</sub> as an additional precursor which does not contain any base.

The results summarized in Fig. 7 show that PdBr<sub>2</sub> failed to effectively deliver the monoester 3MP. This lack of activity may be attributed to catalyst poisoning by the bromide, which likely binds strongly to Pd and inhibits the coordination of butadiene, or by the non-basic character of the bromide anion. Pd(acac)<sub>2</sub> is also a basic precursor but the yield to 3MP was of only 14 %. However, in this case, we expect that the equilibrium between acetylacetonate and acetylacetone would be completely shifted to the latter in the presence of an excess p-TsOH. Also, according to our previous DFT calculations, since the pK<sub>b</sub> of the acac base is even lower than OAc<sup>-</sup>, one expects that the energy profile for the concerted methanolysis would be deeper than the one of OAc<sup>-</sup>, leading to a greater apparent activation energy. In contrast, Pd(TFA)<sub>2</sub> and Pd(OAc)<sub>2</sub> emerged as the most effective precursors for this reaction, very likely because these bases are weaker and they co-exist with their conjugated acid. Notably, Pd(OAc)<sub>2</sub> achieved 75 % monoester formation with minimal isomerization (8 %). This behaviour may be explained by the good compromise between the acid-base character of the OAc<sup>-</sup>/HOAc system. In other words, OAc<sup>-</sup> is more basic that TFA<sup>-</sup>, but it is not basic enough to be completely protonated in the presence of an excess of p-TsOH. Additionally, traces of butenyl ethers (E1 + E2) (< 7 %) were detected across all four precursors (see Table S6 in SI).
<table><caption>**Table 2**
Impact of temperature and reaction time on the mono-methoxycarbonylation of butadiene.</caption><thead><tr><th>Entry</th><th>Time (h)</th><th>T (°C)</th><th>Yield (%) 3MP</th><th>Yield (%) 2MP</th><th>Yield (%) 4MP</th><th>Yield (%) dmα</th><th>Yield (%) E1 + E2</th><th>BD conversion (%)</th></tr></thead><tbody><tr><td>1</td><td>2</td><td>120</td><td>44</td><td>40</td><td>3</td><td>6</td><td>0</td><td>93</td></tr><tr><td>2</td><td>24</td><td>120</td><td>15</td><td>31</td><td>1</td><td>49</td><td>0</td><td>98</td></tr><tr><td>3</td><td>2</td><td>100</td><td>46</td><td>1</td><td>0</td><td>0</td><td>11</td><td>58</td></tr></tbody></table>

Reaction conditions: butadiene (9.2 mmol), MeOH (5.5 eq. with respect to BD), Pd(TFA)₂ (3.0 mol%), d'bpx (6.0 mol%), p-TsOH·H₂O (12.0 mol%), CO (30 bar), toluene (25.0 mL), t (h) at T (°C). The yields were determined by GC analysis with mesitylene as internal standard.

<figure><img src="image_11.png" /><figcaption>**Fig. 7.** Effect of the Pd(II) precursor on the 3MP yield.</figcaption></figure>

From our previous DFT calculations, we would not expect a so high increase of the performance with the contribution of the OAc⁻ base alone (due to the rather low pKₐ of HOAc). However, one must recall that the theoretical modelling of the base and its conjugated acid in methanol is a simplification of the actual reaction medium since, in the catalytic experiments, p-TsOH co-exists with OAc⁻ or TFA⁻, depending on the Pd precursor used. Logically, these species will react with each other and a mixture between the different conjugated acid-bases will be obtained, whose relative amounts will be dependent on their relative pKₐ and the starting concentrations. Nonetheless, if one refers to the reaction conditions reported in the literature for the double alkoxycarbonylation of butadiene, it can be seen that there is an excess of p-TsOH (8 mol%) in comparison to the conjugated base (4 mol% coming from 2 mol% of Pd(TFA)₂) [15]. Hence, we can assume that free p-TsOH will be present in the medium even though a part of this acid will be quenched by TFA⁻ following the equilibrium depicted in Scheme 3.

Therefore, to further explore the role of the acid/base pair in methoxycarbonylation, we conducted a series of experiments employing

different amounts of external acid (x mol%) and base (y mol%). Since the Pd precursor already contains 2 eq. (or 6 mol%) of the base in its structure, we took it into account for calculating the total base amount (y' = y + 6, where y' is the total amount of base). We used para-toluenesulfonic acid monohydrate (p-TsOH·H₂O, pKa = -2.8) in combination with two different bases: sodium acetate (NaOAc) and sodium trifluoroacetate (NaTFA). The results of this study are summarized in Table 3, with Fig. 8 specifically depicting the yields of monoesters for each acid-base pair.

When the reaction is in a strongly acidic environment, ester production remains relatively low (entries 1–3 and 8–9). However, increasing the base concentration significantly enhances the alkoxycarbonylation process, suggesting a promoting and non-innocent role of the base, as the Pd-hydride formation is achieved even if some of the acid is neutralized. Interestingly, the optimal acid-to-base ratio to maximize ester formation depends on the strength of the base. With acetate (pKₐ = 9.2), the maximum yield is reached at a higher p-TsOH concentration (18 mol% p-TsOH vs. 12 mol% OAc, entry 10) than with TFA⁻ (pKₐ = 13.8), which exhibits an optimal acid-base ratio in the presence of an excess of the base (namely 12 mol% p-TsOH vs. 18 mol% TFA⁻, entry 6).

Concerning the side-reaction, in the case of TFA⁻ a neutral to basic environment promotes the formation of butenyl ether byproducts (entries 4, 6 and 7), due to increased nucleophilic attack from the base. However, we demonstrated that these side-products can undergo methoxycarbonylation to 3MP when the reaction is prolonged to 24 h (entry 5). This reactivity is consistent with the C-O cleavage previously noted by another research group in a similar reaction [35]. Butenyl ethers were notably less abundant when OAc⁻ was used as base (entries 11–13).

Additionally, our DFT calculations suggest that the HOAc-OAc⁻ combination presents higher apparent energy barriers (Table 2) due to its lower pKₐ. This behaviour was confirmed upon addition of a large excess of OAc⁻ base with respect to p-TsOH (entries 12–13) or by using HOAc as the unique acid present in the medium under the optimal ratio (18 mol% HOAc vs. 12 mol% OAc⁻, entry 14). Conversely, TFAH-TFA⁻ reaches a reactivity comparable to that of p-TsOH-TFA⁻ when both are used in equivalent concentration (15–15 mol%, entry 15), which is also well-aligned with DFT.

The fact that we observe a synergistic effect by pairing the OAc⁻ base with p-TsOH overtaking these TFAH-TFA⁻ and p-TsOH-TFA⁻ pairs can be explained by the respective involvement of OAc⁻ and p-TsOH in the deprotonation and re-protonation, with a simultaneous proton exchange between them in an additional step to regenerate both species (Scheme 4).

As already mentioned, depending on the relative strength of the acid and base involved, each of this step may be more or less efficient. Moreover, coming back to our DFT calculations, our hypothesis may

<figure><img src="image_12.png" /><figcaption>**Scheme 3.** Proton exchange equilibrium between p-TsOH and TFA⁻.</figcaption></figure>
<table><caption>**Table 3**
Products distribution obtained for different Pd precursors and various acid-base ratios.</caption><thead><tr><th>Entry</th><th>[Pd] precursor</th><th>Time (h)</th><th>Acid-base pair</th><th>(x-y') mol%</th><th>Yield (%) 3MP</th><th>Yield (%) (2MP + 4MP)</th><th>Yield (%) (E1 + E2)</th></tr></thead><tbody><tr><td>1</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>24-6</td><td>9</td><td>0</td><td>5</td></tr><tr><td>2</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>20-10</td><td>11</td><td>0</td><td>3</td></tr><tr><td>3</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>18-12</td><td>21</td><td>0</td><td>6</td></tr><tr><td>4</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>15-15</td><td>46</td><td>0</td><td>47</td></tr><tr><td>5</td><td>Pd(TFA)<sub>2</sub></td><td>24</td><td>p-TsOH-TFA<sup>-</sup></td><td>15-15</td><td>80</td><td>16</td><td>0</td></tr><tr><td>6</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>12-18</td><td>53</td><td>0</td><td>41</td></tr><tr><td>7</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>p-TsOH-TFA<sup>-</sup></td><td>6-24</td><td>25</td><td>0</td><td>60</td></tr><tr><td>8</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>24-6</td><td>25</td><td>0</td><td>14</td></tr><tr><td>9</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>20-10</td><td>47</td><td>3</td><td>9</td></tr><tr><td>10</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>18-12</td><td>71</td><td>23</td><td>1</td></tr><tr><td>11</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>15-15</td><td>63</td><td>21</td><td>0</td></tr><tr><td>12</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>12-18</td><td>5</td><td>0</td><td>25</td></tr><tr><td>13</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>p-TsOH-OAc<sup>-</sup></td><td>6-24</td><td>2</td><td>0</td><td>3</td></tr><tr><td>14</td><td>Pd(OAc)<sub>2</sub></td><td>2</td><td>HOAc-OAc<sup>-</sup></td><td>18-12</td><td>2</td><td>0</td><td>5</td></tr><tr><td>15</td><td>Pd(TFA)<sub>2</sub></td><td>2</td><td>TFAH-TFA<sup>-</sup></td><td>15-15</td><td>41</td><td>0</td><td>42</td></tr></tbody></table>

<figure><img src="image_13.png" /><figcaption>**Fig. 8.** Effect of the acid to base ratio on the yield in all monoesters (2MP + 3MP + 4MP).</figcaption></figure>

have a significant impact on the kinetic interpretation. Indeed, if we assume that this equilibrium for the acid-base regeneration step is fast, the acid/base pair (OAc⁻ and p-TsOH) involved in steps 4 to 6 should be regenerated after step 6. Although this equilibrium is naturally displaced to the left according to relative pKₐ/pKₐ values, the fact that HOAc and p-TsO⁻ accumulate on the medium as reaction progresses would partially shift the regeneration to the right. Consequently, the deprotonation steps 4 and 5, will be catalyzed by OAc⁻ (the stronger base) and the re-protonation step 6 will occur more rapidly with the stronger acid p-TsOH (and not with HOAc). If so, the apparent kinetic energy should be calculated by considering L-p-TsOH for TDI (−138 kJ mol⁻¹) and E as TDTS (+12 kJ mol⁻¹), leading to 67 kJ mol⁻¹, which may explain the highest performances observed by combining both additives. On the other hand, a too large excess of OAc⁻ might reduce p-TsOH concentration, which is strongly detrimental for the re-protonation step and thus to the catalytic activity as shown in Fig. 8. Nevertheless, one must note that this estimation does not consider the relative concentration of p-TsOH and OAc⁻, which will impact the regeneration equilibrium.

If we consider a weaker base such as TFA⁻, it is expected that the relative concentrations will be less determinant particularly for a large excess of the base, as it can be observed from our DFT calculations. In

that case, a lower acid/base ratio is required to reach the optimal concentration.

Thus, combining our experimental and theoretical approach, we propose the following base-assisted mechanism for the methoxycarbonylation of butadiene to 3MP (Scheme 5).

This mechanism elapses through the formation of a Pd(0) species, which is then re-protonated by the acid to generate the corresponding Pd(II) hydride. This is a strong difference with respect to the generally accepted mechanism, in which an oxidation state of +2 remains constant for Pd during the whole reaction. Interestingly, most studies report good to excellent catalytic activity when starting from either Pd(0) or Pd(II) precursors [2], with the latter typically requiring an in-situ reduction to Pd(0), prior to oxidative protonation to yield the cationic Pd-H active species [36–38]. This step would generate (d'bpx)Pd(CO) complex L which in our case is involved in the catalytic cycle. Although the reaction pathway for reductive pre-activation still remains to be elucidated, it is well known that Pd(II) is more easily reduced in basic medium [39]. Overall, one should note that alkoxycarbonylation is often accompanied by formation of metallic Pd or nanoparticles, and that in some cases Pd nanoparticles have been demonstrated to be a suitable metallic precursor for the reaction [40]. In these terms, the fact that a Pd
<figure><img src="image_14.png" /></figure>

<figure><img src="image_15.png" /></figure>

<figure><img src="image_16.png" /><figcaption>**Scheme 4.** a) Methanol deprotonation, b) Pd(0) re-protonation, c) additional step: proton exchange between the acid-base pair.</figcaption></figure>

(0) species is involved in the catalytic cycle would not be in contradiction with both the formation of Pd black and the redissolution of metallic Pd in the presence of an acid.

### 3. Conclusion

The following conclusions can be deduced from this work after combining our theoretical and experimental findings on the monomethoxycarbonylation of butadiene catalyzed by a hydride ($d^tbpx$)Pd-complex.

* After benchmarking cautiously our choices regarding the hypothesis of the DFT calculations against CCSD(T) and experimental data, we undertook a systematic DFT study of the mechanisms and Gibbs free energy profile using an implicit solvent. The energy profiles combined with energetic span analysis revealed a significant apparent activation energy of 202 kJ·mol⁻¹ associated to the methanolysis step (160 kJ·mol⁻¹ in presence of 3 methanol molecules cluster). This high barrier, incompatible with experimental knowledge, raised severe questions about the concerted mechanisms proposed before.

* The energetic span analysis identifies that the TOF-determining intermediate is the Pd($\eta^3$-allyl) complex (and not a $\sigma$-allyl). In addition, we confirmed by NMR spectroscopy the existence of this important intermediate.

* For the DFT modelling, it is crucial to consider the proper solvent present in the surrounding of the different components of the systems. To be consistent with our experimental observations, we proposed a simplified model in which reaction intermediates are solvated in toluene, whereas acid and bases are solvated in methanol. We suggest that future theoretical works might investigate how a micro-solvation model combining methanol molecules in explicit toluene solvent may impact the result presented here.

* DFT simulations showed that the non-innocent base induces a significant decrease of the apparent activation energy (down to about 100 kJ·mol⁻¹) due to a lower TDTS energy level involved in methanalysis, while keeping the same Pd($\eta^3$-allyl) complex as TDI. Such a value becomes more compatible with a reaction taking place at 100 °C. Experimentally, we confirmed that monovalkoxycarbonylation of butadiene to **3MP** is fast at 100 °C, and full conversion can be obtained after few hours.

* The base-assisted mechanism challenges the traditional Pd-hydride mechanism, which usually assumes a base-free process and a constant Pd(II) oxidation state throughout the catalytic cycle. Instead, we have proposed a revised mechanism where the presence of a base facilitates changes in Pd oxidation state during methanolysis, following the reductive and elimination of the ester. Moreover, we showed that the energetics of some steps (deprotonation, re-

<figure><img src="image_17.png" /><figcaption>**Scheme 5.** Proposed mechanism for the multiple acid and base-assisted methoxycarbonylation of BD to **3MP**.</figcaption></figure>
protonation, and methanolysis) is directly tuned by the relative strengths of the acid/base pair which is present in the medium.

* We showed that changing the nature of acid/base mixtures based on p-TsOH-TFA⁻ or p-TsOH-OAc⁻ impacts the reaction conversion and selectivity. Our best results were obtained using the OAc⁻/p-TsOH mixture with a relative molar ratio of 0.66. Under these conditions, the reaction rate was improved and full conversion to monoesters was obtained after only 2 h reaction at 100 °C. This synergy effect between OAc⁻ and p-TsOH was proposed to be explained by the combined role of the OAc⁻ base and p-TsOH acid. While OAc⁻ is directly involved in the methanol deprotonation and assisted methanalysis steps, p-TsOH re-protonates the Pd catalytic site. Simultaneously, a rapid proton exchange between HOAc and p-TsO⁻ would take place to regenerate the OAc⁻ and p-TsOH species. Assuming no kinetic limitation preventing this acid/base proton transfer, this proposal together with the DFT energy profiles may explain why the relative concentration of the acid/base as well as their respective pKₐ/pKₛ influence the experimental yields in monoesters.

# 4. Experimental section

## 4.1. DFT methods

All energy calculations were performed by using Gaussian 16 [41] quantum computational software. Optimized structures were achieved by using the TZVP [42] basis set for P, C, F, S, O, and H, and LANL2DZ [43] including effective core potential (ECP) [44] for Pd, after the structures had been preoptimized using LANL2DZ for Pd and 6-31 g* basis set for the remaining atoms to reduce computational cost. The LANL2DZ basis was previously shown to be relevant for the analogous Pd-catalyzed alkene alkoxycarbonylation [21]. Regarding the exchange-correlation functional, as justified by the various benchmarks described in sections 1.1.1 and 1.1.2 of the Supporting Information, we chose the ωB97XD [45] functional which represents the best compromise, delivering energy values closest either to the CCSD(T) [46] reference or to experimental one for CO coordination and for CO insertion into a Pd-alkyl bond.

Thermal and entropic corrections were included according to standard statistical thermodynamics. Transition states (TS) were obtained through energy scans and then refined by carrying out single-point energy calculations (Berny algorithm). Systematic harmonic vibrational frequency analyses have been employed to confirm that all TS structures exhibit one unique imaginary frequency while all intermediates exhibit real frequencies. All Gibbs free energies and enthalpies are expressed in kJ·mol⁻¹ assuming a temperature of 298.15 K and pressure of 1 atm. We use the CPCM solvation model to describe toluene (ε = 2.3741) and methanol (ε = 32.613) as implicit solvent of the various components of the catalytic system and its environment (refer to section 1.1.3 in the SI).

## 4.2. Experimental methods

Unless otherwise specified, reactions were conducted under an argon atmosphere using standard Schlenk techniques or MBraun Ar-atmosphere glovebox. Glassware was dried in an oven for at least 15 h. Solvents were purchased from Sigma Aldrich and further purified using an SPS-MBraun system. Water content of the solvents has been controlled by Karl-Fischer coulometry using a microcoulometer Methrom 756 KF. All chemicals were obtained from Fisher Scientific and stored in the glovebox. d'bpx was obtained from Sigma-Aldrich.

NMR spectra were recorded on Bruker AC 300 MHz at 293 K (or 298 K) unless otherwise stated. Chemical shifts δ (ppm) are given relative to CDCl₃. Signals were assigned as s (singlet), d (doublet), t (triplet), dd (doublet of doublet), m (multiplet) and bs (broad singlet). All measurements were carried out at room temperature unless otherwise stated. The outcome of every catalytic test has been analyzed using a HP-PONA column (Agilent 6850 series II) (polymer of ramified

methylsilicone) of 50 m length (internal diameter of 0.2 mm and 0.5 µm of film thickness), and an FID detector. For chemical identification, GC-MS analyses were conducted with an Agilent 6890 N apparatus with a PONA and an Agilent 5975B inert XL EI/CI MSD mass spectrometer. The products are identified by comparison with the pre-existing library of chromatograms of standard compounds. Finally, retention times for the different products were determined after injection of a solution of the corresponding pure molecules. An example of a typical chromatogram after a catalytic reaction is given in Fig. S10.

### 4.2.1. Alkoxycarbonylation procedure

The catalytic tests for the alkoxycarbonylation of butadiene were performed in a 100 mL stainless-steel reactor. Initially, the reactor was loaded with p-TsOH·H₂O, sodium acetate (NaOAc) or sodium trifluoroacetate (NaTFA), when necessary, and a stirring bar, followed by purging with three cycles of vacuum/argon. In a glovebox, a Schlenk flask was charged with Pd(TFA)₂ (3.0 mol%) and the diphosphine ligand (d'bpx) (6.0 mol%), then 15 mL of toluene was added, and the mixture was stirred at room temperature under an argon atmosphere for 20 min. The reactor was then injected with 10 mL of toluene, followed by the prepared catalyst solution. Next, 2.1 mL of methanol (5.5 equivalents relative to the substrate) and 9.24 mmol of butadiene (from a commercial 20 wt% solution in toluene) were added. The reactor was pressurized to 26 bars with CO and heated to either 100 °C or 120 °C. Upon reaching the desired temperature, the pressure increased to 30 bar, and the reaction proceeded for 2 h. After completion, the reactor was cooled to -10 °C, depressurized, and a sample was taken for analysis after the addition of the internal standard. Quantitative analysis was carried out with GC-FID, using mesitylene as an internal standard.

### 4.2.2. Pd(II) precursor screening

The methodology was the same described for the general alkoxycarbonylation reaction, but in this case a Schlenk flask was charged with the corresponding Pd precursor (3.0 mol%) and the diphosphine ligand (d'bpx)(6.0 mol%), then 15 mL of toluene was added, and the mixture was stirred at room temperature under an argon atmosphere for 20 min. The reactor was then injected with 10 mL of toluene, followed by the prepared catalyst solution. Note that in these experiments no external base was used.

### 4.2.3. Synthesis of [Pd(1,2-bis-ditert-butylphosphinomethylbenzene)(η³-but-3-enyl)] complex

Initially, an oven-dried Schlenk was loaded with p-TsOH·H₂O (12.0 mol%, 0.55 mmol), Pd(TFA)₂ or Pd(OAc)₂ (3.0 mol%, 0.14 mmol), and the diphosphine ligand (d'bpx) (6.0 mol%, 0.28 mmol). Toluene (10 mL) was then introduced, followed by methanol (5.5 equivalents with respect to BD, 25.42 mmol). Finally, butadiene (4.62 mmol, solution in toluene) was added. The reaction mixture was then stirred at 100 °C for 2 h. The product was analyzed by ¹H and ³¹P NMR and the set of signals was compared with those reported on the literature for the same complex prepared by a different methodology [9].

¹H NMR (300 MHz, CDCl₃, 298 K): δ 7.24-7.44 (m, 4H, aromatic CH), 6.56 (m, 1H, Hc), 5.30 (m, 1H, Hb), 4.64 (m, 1H, Ha), 3.84-3.60 (m, 4H, benzylic CH₂), 3.34 (m, 1H, Ha'), 1.47-1.20 (m, 59H, tBu-H and Hd). ³¹P{¹H} NMR (300 MHz, CDCl₃, 298 K): δ 50.1 (d, ²Jpp = 39.2, Pa), 43.03 (bs, Pb).

## Funding sources

This work was funded by IFP Energies Nouvelles.

## CRediT authorship contribution statement

**Mohammad Ameskal:** Writing – original draft, Investigation, Formal analysis.
**Lionel Magna:** Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation,
Formal analysis, Data curation, Conceptualization. **Juan M. Asensio:**
Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. **Pascal Raybaud:** Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

The authors thank IFP Energies Nouvelles for the financial support of the PhD thesis and for providing access to its HPC (ENER 440) where all calculations have been undertaken.

Appendix A. Supplementary data

Some detailed discussion on the choice of DFT level of theory, relative energies of reaction intermediates, details about the solvation model, and NMR spectra are given in the *Supporting Information*. Cartesian coordinates for optimized DFT structures are also included. Supplementary data to this article can be found online at https://doi.org/10.1016/j.jcat.2025.116235.

Data availability

Data will be made available on request.

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