Catalysis to React Carboxylic Acids with Isonitriles under Mild Conditions

Abstract

Previous research has shown that isonitriles and carboxylates react in a simple two-component coupling (2cc) reaction to form homogenous N-linked glycoproteins via 1,3 O N acyl transfer. However, activating the reaction required heating the reaction mixture in a microwave to 150 °C. Our research proposed to overcome the problem of high activation energy by finding a suitable iron-based catalyst. We aimed to synthesize an iron half-sandwich complex with two phosphine ligands, to allow for control over the sterics and electronics of the catalyst, and we included an hydrogen-bonding residue to facilitate the 1,3 O N acyl transfer. We successfully synthesized the desired target complex [CpFe(PMe3)(3-pyPPh2)(CyNC)][PF6], but could not isolate it in high purity. Upon further investigation, it was found that the ligands of [CpFe(PMe3)(3-pyPPh2)(CyNC)][PF6] redistribute in solution, precluding its isolation in high purity. We proceeded with studies of the reaction of [CpFe(PMe3)(3-pyPPh2)(CyNC)][PF6] with propionic acid, and observed no reaction between the complex and propionic acid. Attempts to carefully oxidize the complex from Fe2+ to Fe3+ in the absence of any excess CyNC yielded a stable Fe3+ derivative, but this complex also appeared not to react with propionic acid. Other efforts to synthesize a capable and inherently less electron rich catalyst candidate, [CpFe(CyNC)(CO)2][PF6], were successful. After isolating the complex, studies did not appear to show any reactivity with carboxylates. Future studies will look to oxidizing the iron in [CpFe(CyNC)(CO)2][PF6] to Fe3+, which will hopefully make the complex electron poor enough to induce nucleophilic attack on the coordinated isonitrile.