Synthons by Catalytic Oxidative Carbonylation of Arenes: From Polymers to Pharmaceuticals

The carbonylation of arenes can be used to produce synthons used to make a variety of products ranging from polymers to pharmaceuticals. The most active catalysts for arene carbonylation are based on rhodium and palladium in the presence of a vanadium co-catalyst. The aim of this work was to elucidate the mechanism by which complexes of rhodium and palladium promote the carbonylation of arenes and to establish the influence of both arene and ligand composition on catalytic activity and selectivity. The Rh-catalyzed arene oxidative carbonylation is initiated by the coordination and subsequent C-H bond activation of the arene to the complex Rh(CO) 2(TFA)3. CO migratory insertion followed by reductive elimination yields mixed anhydrides of the desired aromatic acid. Reaction conditions were optimized in order to obtain high yields and to provide evidence for the steps proposed in the catalytic cycle. A catalytic cycle involving molecular oxygen was identified for the vanadium co-catalyst required for re-oxidation of Rh(I) to Rh(III). Evidence for the species proposed in the mechanism was acquired using NMR, IR, and UV-Visible spectroscopy. The active form of the Rh(CO)2(TFA)3 catalyst was identified by these means and involves two cis-positioned carbonyl ligands, which exhibit an unusual interaction with the trifluoroacetate ligands to form a five-membered ring. Spectroscopic evidence for this form of the active form of the catalysts was strongly supported by density functional theory calculations. A mechanism similar to that found for Rh-catalyzed oxidation of arenes was identified for the Pd-catalyzed system. In this case, the active species is a Pd(II) complex, which in the course of reaction is reduced to a Pd(0) complex. The Pd complex typically exhibits higher activity but lower para selectivity than the Rh complex. It was possible to tune the activity of both the Pd and the Rh catalysts by altering the ligands present on the complex. Chlorodifluoroacetate ligands provided the highest activity for Rh complexes, whereas trifluoroacetate ligands provided the highest activity for Pd complexes. The observed dependence of activity on ligand composition was attributed to a balance between the ability of the metal to coordinate to the arene, favored by electron withdrawing ligands, and the ability of the ligand to abstract a proton, favored by more basic ligands. In a complementary study, the oxidation of benzotrifluoride to benzoyl fluoride using a niobium catalyst in the presence of carboxylic or sulfonic acids was investigated. The composition of the acid was found to play two roles---as a proton source to activate the C-F bond and as an oxygen transfer agent to form benzoyl fluoride. Oxygen facilitated fluorine transfer but did not enter into the reaction products. A mechanism for the conversion of benzotrifluoride to benzoyl fluoride was proposed.