Catalytic Oxidative Decarboxylation of Amino Acids

Amino acids are inherent precursors of functionalized bulk chemicals: their molecular structure contains several functionalities, especially a carboxylic acid as well as an amine functional group on the same carbon atom. Nowadays, amino acids are not only available from chemical synthesis or large-scale fermentation processes, but even protein-rich rest streams from agro-industry can be considered as potential and relatively cheap sources.[1] During the valorization process of these waste streams, hydrolysis of isolated proteins results in an aqueous mixture of amino acids. However, separation of the individual amino acids is rather difficult, due to their pH-dependent charge behavior. [2] Oxidative decarboxylation of amino acids into the corresponding nitriles might be a useful chemical transformation to circumvent the separation issues. Moreover, nitriles are interesting starting compounds, as their chemical modification gives access to several other functionalized intermediates. The oxidative decarboxylation of amino acids is mediated by hypobromite (‘Br+’) species, which are available from classical organic reagents like N-bromosuccinimide.[3] Active hypobromite species can even be generated in situ, via oxidation of sodium bromide by sodium hypochlorite.[4] However, these methods produce stoichiometric amounts of (in)organic waste products, respectively succinimide and sodium chloride. On the other hand, it has been shown that the vanadium chloroperoxidase enzyme is able to perform the oxidative decarboxylation of L-glutamic acid and L-phenylalanine with hydrogen peroxide as a green oxidant.[5] Based on previous work on olefin epoxidation[6], a tungstate-exchanged layered double hydroxide (LDH) has been developed as a heterogeneous mimic of the enzyme’s active site: tungstate ions are in situ transformed by hydrogen peroxide into peroxotungstate species, which are immobilized onto the LDH surface and in turn oxidize bromide ions to hypobromite species. Therefore, the amino acid is dissolved in acetonitrile containing catalyst particles and ammonium bromide. To suppress the formation of singlet oxygen from peroxotungstate, it is necessary to add diluted hydrogen peroxide in a controlled way to the reaction mixture. The catalyst material is stable under reaction conditions and can be recycled by centrifugation. L-Phenylalanine can be transformed into benzyl cyanide in almost quantitative yield with 8 equivalents of H2O2. The oxidant efficiency might be increased by subtle modifications of the catalytic system. The substrate scope has already been extended to aliphatic amino acids like L-valine, L-leucine and L-isoleucine, with 60-80% yield of the corresponding nitriles. Further research is ongoing to extend the substrate scope towards other natural amino acids containing additional functional groups (-OH, -NH2, -COOH, -CONH2 …).status: publishe