Modeling the effect of ligands and solvation on hydrolysis variants in the Pd(II)-Catalyzed hydroxycarbonylation of pentenoic acids

Highlights

• Hydrolysis step crucial for Pd-catalyzed hydroxycarbonylation of pentenoic acids.

• Hydrolysis mechanism (stepwise vs concerted) varies with number of H₂O molecules.

• Pd-catalyst with diphosphine ligand prefers concerted mechanism with 1H₂O.

• Stepwise pathway preferred with 2 and 3H₂O molecules.

• Solvent effect has a major influence on the nature of the product.

Abstract

We explored computationally variations in the hydrolysis step of the Pd(II)-catalyzed hydroxycarbonylation of pentenoic acids for several ligands L₂ = 1,2-bis[(di-R)phosphinomethyl]benzene where R = tert-butyl, methyl, or phenyl, referring to these ligands by DTBPX, DMPX, and DPPX, respectively. Thus far, most computational models invoked three H₂O molecules in the crucial step which can occur in either a concerted or a stepwise fashion. We used density functional calculations to study systematically the effect of the number of water molecules (H₂O)_m, m = 1–3, on the nature of the crucial step, concerted vs stepwise. Accordingly, the concerted mechanism is preferred over the stepwise mechanism for m = 1. For m = 2, the stepwise mechanism is preferred for the ligand DTBPX, and the concerted mechanism for the ligands DMPX or DPPX. For m = 3, the stepwise mechanism is preferred for all three ligands under study and, importantly, also results in the overall lowest hydrolysis barriers. An energy decomposition analysis of these hydrolysis barriers, evaluating corrections due to larger basis set, dispersion interaction, and solvation, indicates that the latter term indeed is responsible for rendering adipic acid the most likely product.

Introduction

Transition-metal-mediated alkene transformations are well-known to play a key role in synthesizing industrially important products. Reactions involving the carbonylation of alkenes to generate acyl complexes are noteworthy examples [1,2]. The hydroxycarbonylation, which belongs to this important class of reactions, is one of the most common homogeneously catalyzed reactions in the chemical industry [[3], [4], [5], [6]]. Recently, Meurs and co-workers reported [7,8] the hydroxycarbonylation of pentenoic acids (PEAs) catalyzed by a Pd(II) catalyst bearing the bulky ligand L₂ = 1,2-bis[(di-R)phosphinomethyl]benzene, DTBPX, with R = tert-butyl. This catalyst achieves a selectivity of over 95% toward the linear product, adipic acid (ADA), in comparison to the branched regio-isomers methyl glutaric acid (MGA), ethyl succinic acid (ESA), and propyl malonic acid (PMA) [[7], [8], [9], [10], [11], [12]], Scheme 1, Scheme 2.

For Pd(II) catalysts bearing less bulky ligands L₂ of the same overall composition, but with the substituents R = methyl (L₂ = DMPX) or phenyl (L₂ = DPPX), the branched products PMA (75%) and ESA (90%) become more favorable [12]. The proposed mechanism [12] consists of three major steps: (i) substrate isomerization, (ii) CO insertion, and (iii) hydrolysis, Scheme 1. Hydrolysis, the rate determining step, was studied computationally using a (H₂O)₃ cluster for the concerted pathway, which is analogous to the approach for methanolysis, with three methanol molecules, (CH₃OH)₃ [11]. Furthermore, in that study [12] a stepwise pathway was proposed, comprising a hydration step followed by product release, Scheme 2; see also Scheme S1 in the Supplementary Data (SD) of the present work.

DFT modeling [12] showed that the active catalyst [L₂Pd^II–H]⁺ isomerizes the PEAs to their equilibrium mixture of Pd(II)-alkyl intermediates, from which carbonylation leads to a stable Pd(II)-acyl complex, Scheme 1. Subsequent hydrolysis of the latter complex results in the formation of linear or branched products. For the crucial hydrolysis step, the calculated barriers decreased significantly when the number of participating H₂O molecules increased from 1 to 3, (H₂O)_m, m = 1–3, with m = 3 being the optimum number of water molecules [12]. The free energy barriers for the hydrolysis step essentially do not change for n = 4 where the added H₂O molecule acts as a spectator or a solvent [12]. Using a (H₂O)₃ cluster was determined to favor the stepwise mechanism over the analogous concerted variant of the hydrolysis of the Pd-acyl complexes [12]. For the ligand DTBPX, the upper free energy barrier of the stepwise hydrolysis is by 42 kJ mol⁻¹ higher (109–67 kJ mol⁻¹) than the barrier of the concerted hydrolysis step leading to ADA, Scheme 1. The hydrolysis step exhibited a preference for the product ADA for all ligands, at variance with the experimentally observed selectivity for the branched products PMA and ESA for less bulky DMPX, and DPPX ligands [12].

The goal of the present computational work is to evaluate the preferential hydrolysis mechanism, concerted vs stepwise with the number of water molecules (H₂O)_m, m = 1, 2, followed by a comparison with the recently reported hydrolysis using a (H₂O)₃ cluster [12]. For the calculated rate-limiting hydrolysis barriers (concerted or stepwise), we analyzed the contribution of various energy terms – corrections due to larger basis set, inclusion of dispersion interactions, and solvation – to understand how each of these terms is affecting the decision between branched vs linear products.