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Palladium-catalyzed alkoxycarbonylation reactions allow for the efficient conversion of widely available unsaturated compounds, CO and alcohols into the corresponding carboxylic acid derivatives. A driving force for the development of new and improved catalytic methodologies is the design and synthesis of ligands, which fine-tune the properties of the metal center. In general, alternation of the ligand backbone and substituents adjusts the electronic and steric properties of the active catalyst species to control activity and selectivity of a given catalytic process. Therefore, our group has a long-standing interest in ligand developments. In the past decade, several classes of ligands have been developed by us for palladium-catalyzed carbonylation reactions, which are summarized in this article. As an example, mono- and bidentate phosphines with heteroaromatic backbones were prepared to overcome the limitations of known catalyst systems. The common feature of all these ligands is the function of the integrated base, which acts as a proton shuttle for the formation of the palladium hydride and the rate-determining N-assisted alcoholysis. On the other hand, the basic substituent improves the durability of the catalyst via hemilabile coordination to the palladium center in the catalytic cycle.

The first active catalyst system for the carbonylation of tri- and tetra-substituted olefins with paraformaldehyde and methyl formate is described. Specifically, using 1.0 mol% Pd(OAc)2 and 4.0 mol% 1,2-bis-(tert-butylpyridylphosphino)xylene L3 in the presence of 5.0 mol% PTSA·H2O, and 0.5 mol% Pd(OAc)2 and 2.0 mol% L3 in the presence of 8.0 mol% PTSA·H2O, respectively, allowed the corresponding linear esters to be obtained in good yields and selectivities.

A general and selective palladium-catalyzed alkoxycarbonylation of all kinds of alkenes with formic acid (HCOOH, FA) is described. Terminal, di-, tri-, and tetra-substituted including functionalized olefins are converted into linear esters with high yields and regioselectivity. Key-to-success is the use of specific palladium catalysts containing ligands with built-in base, e.g., L5. Comparison experiments demonstrate that the active catalyst system not only facilitates isomerization and carbonylation of alkenes but also promotes the selective decomposition of HCOOH to CO under mild conditions.

Mechanistic studies of the catalyst [Pd2(dba)3/1,1′-bis(tert-butyl(pyridin-2-yl)phosphanyl)ferrocene, L2] for olefin alkoxycarbonylation reactions are described., Mechanistic studies of the catalyst [Pd2(dba)3/1,1′-bis(tert-butyl(pyridin-2-yl)phosphanyl)ferrocene, L2] for olefin alkoxycarbonylation reactions are described. X-ray crystallography reveals the coordination of the pyridyl nitrogen atom in L2 to the palladium center of the catalytic intermediates. DFT calculations on the elementary steps of the industrially relevant carbonylation of ethylene (the Lucite α-process) indicate that the protonated pyridyl moiety is formed immediately, which facilitates the formation of the active palladium hydride complex. The insertion of ethylene and CO into this intermediate leads to the corresponding palladium acyl species, which is kinetically reversible. Notably, this key species is stabilized by the hemilabile coordination of the pyridyl nitrogen atom in L2. The rate-determining alcoholysis of the acyl palladium complex is substantially facilitated by metal–ligand cooperation. Specifically, the deprotonation of the alcohol by the built-in base of the ligand allows a facile intramolecular nucleophilic attack on the acyl palladium species concertedly. Kinetic measurements support this mechanistic proposal and show that the rate of the carbonylation step is zero-order dependent on ethylene and CO. Comparing CH3OD and CH3OH as nucleophiles suggests the involvement of (de)protonation in the rate-determining step.

A general palladium-catalyzed synthesis of linear esters directly from sec- and tert-alcohols is described. Compared to the classic Koch–Haaf reaction, which leads to branched products, this new transformation gives the corresponding linear esters in high yields and selectivity. Key for this protocol is the use of an advanced palladium catalyst system with L2 (pytbpx) as the ligand. A variety of aliphatic and benzylic alcohols can be directly used and the catalyst efficiency for the benchmark reaction is outstanding (turnover number up to 89 000).

The development of ligands plays a key role and provides important innovations in homogeneous catalysis. In this context, we report a novel class of ferrocenyl phosphines for the alkoxycarbonylation of industrially important alkenes. A basic feature of our ligands is the combination of sterically hindered and amphoteric moieties on the P atoms, which leads to improved activity and productivity for alkoxycarbonylation reactions compared to the current industrial state-of-the-art ligand 1,2-bis((di-tert-butylphosphino)methyl)benzene). Advantageously, palladium catalysts with these novel ligands also enable such transformations without additional acid under milder reaction conditions. The practicability of the optimized ligand was demonstrated by preparation on >10 g scale and its use in palladium-catalyzed carbonylations on kilogram scale.