A General, Activator‐Free Palladium‐Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid

Abstract

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.

Controlling the Depolymerization of Paraformaldehyde with Pd–Phosphine Complexes

“…The chemical shift of an atom depends on the electron density around the nucleusa nd thus the chemical shift can be used as an indicator for the electron density at as pecific atom. Consequently, 17 ONMR spectroscopy was used to investigate the electron density at the coordinating oxygen atoms.…”

“…To investigate the change in electron density,a gain ac ombination of DFT calculations andN MR measurements was used. To find out about the electron density at thec oordinating oxygen atoms (illustrated in Figure3) 17 ONMR spectroscopy was combinedw ith Voronoi density deformation( VDD) values from DFTc alculations. VDD is-justl ike Mullikan charges-a concept to describe formal chargesa ti ndividual atoms.…”

“…Unfortunately, 17 Oh as al ow natural abundance and low NMR sensitivity so that reasonable signals can only be obtained for pure substances or 17 Oe nriched samples. As an example to link theoretical VDD values and 17 ONMR shifts [Pd(d t bpx)(MeOH) 2 ] 2 + was measured in 17 Oe nriched methanol.…”

“…Important CO surrogates include (para)formaldehyde [13][14][15] and formic acid. [16,17] Most often these "CO-free" carbonylation reactions are catalyzed by late transition metals like Pd or Rh coordinated by phosphine ligands. The catalystp erformst wo important tasks: Firstly,i tc atalyzes the decomposition of the CO surrogate molecule into aC Oe quivalent speciesa nd secondlyi tc atalyzes the actualc arbonylation reaction using the prior generated CO equivalent.…”

“…This study focusses on the depolymerization of paraformaldehyde and the influence of the commonly used carbonylation catalysts [Pd(d t bpx)] 2 + (d t bpx = 1,2-Bis(di-tert-butylphosphinomethyl) benzene) and[ Pd(dppp)] 2 + (dppp = 1,3-Bis(diphenylphosphino) propane) on this depolymerization reaction. By using a combination of in situ Ramans pectroscopy, 1 H, 31 P, and 17 ONMR spectroscopy as well as density functional theory (DFT) calculations we show that [Pd(d t bpx)] 2 + based complexesr aise the activatione nergy for the paraformaldehyde depolymerization by more than two times and that this surprisingr esult can be explained by the complexation behavior of [Pd(d t bpx)] 2 + fragments towards the chain end of the paraformaldehyde molecule. We show that this coordination lowerst he electron density at important oxygen atoms which in turn inhibits the depolymerization reaction.…”