Biomimetic Oxidative Decarboxylation of α-Amino Acids Induced by a Tungstate Based Heterogeneous Catalyst and H2O2 as Terminal Oxidant (2014)

α-Amino acids are inherent precursors of functionalized bulk chemicals, e.g. diamines, diacids, amino alcohols. Nowadays, they are not only abundantly available via large-scale microbial fermentation or biocatalytic synthesis with isolated enzymes, but even protein-rich waste streams from agro-industry and biofuel production constitute relatively cheap sources.[1] During the valorization process of these waste streams, hydrolysis of isolated proteins results in an aqueous mixture of amino acids. Although electrodialysis is considered as potential separation technique for these zwitterionic compounds, only 3 major fractions consisting of neutral, acid and basic amino acids are obtained.[2] Therefore, oxidative decarboxylation of α-amino acids into the corresponding nitriles might be a useful chemical transformation to circumvent the separation issues. Moreover, nitriles are interesting platform molecules to access other functionalized intermediates, e.g. amines, amides, acids. Oxidative decarboxylation of α-amino acids is generally mediated by hypobromite (‘Br+’) species, which are produced from organic reagents like N-bromosuccinimide[3] or by NaOCl induced oxidation of NaBr.[4] However, these methods produce large amounts of (in)organic waste products, respectively succinimide and NaCl. On the other hand, it has been shown that the enzyme vanadium chloroperoxidase is able to perform the oxidative decarboxylation of L-glutamic acid and L-phenylalanine with hydrogen peroxide (H2O2) 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: electrostatically immobilized tungstate ions are transformed in situ by H2O2 into peroxotungstate species, which in turn oxidize bromide ions to hypobromite species. A catalytic system containing LDH and NH4Br in an organic solvent or even water allows selective oxidative decarboxylation of α-amino acids into nitriles, whereas in enzyme-catalyzed reactions selectivity is reduced due to aldehyde formation. Diluted H2O2 is added in a controlled way to suppress the formation of singlet oxygen from peroxotungstate. In this way, L-phenylalanine can be transformed into phenylacetonitrile with 88% yield using 8 equivalents of H2O2. The catalyst material is stable under reaction conditions and can be recovered by centrifugation. The substrate scope has been extended to other natural and non-natural α-amino acids. L-Alanine, L-valine, L-leucine, L-isoleucine and D-norleucine were converted into aliphatic nitriles with 88-100% yield. Moreover, the system is compatible with alcohol, amide and carboxylic acid moieties: the corresponding nitriles from L-serine, L-threonine, DL-homoserine and L-glutamic acid were obtained with >95% yield. Neutralization of carboxylic acids and amines with respectively NaOH or HCl prior to decarboxylation is recommended. In this way, 5-aminopentanenitrile was identified as the major product with fair yield from L-lysine hydrochloride. α-Amino acids containing a phenol or heteroaromatic moiety, e.g. L-tyrosine, L-tryptophane, L-histidine were prone to oxidative ring bromination, whereas only sulphur oxidation was observed in case of L-methionine.