pH-Dependent Chemoselective Synthesis of α-Amino Acids. Reductive Amination of -Keto Acids with Ammonia Catalyzed by Acid-Stable Iridium Hydride Complexes in Water

摘要

Increasing environmental awareness makes it necessary to develop a sustainable synthesis of α-amino acids without the use of highly toxic agents such as cyanides. In this context, reductive amination of α-keto acids has merited special attention, because it is a close laboratory analogy of a pathway by which amino acids are chemoselectively biosynthesized with aqueous NH_3 that is an essential amine source in natural systems. In the nonenzymatic synthesis of α-amino acids, however, catalytic reductive amination has so far been carried out using amine sources other than NH_3 in organic solvents. Thus, catalytic reductive amination of α-keto acids with aqueous NH3 has yet to be achieved. The difficulty of such reactions mainly arises from the use of water as a reaction media. The aqueous media must be acidic enough for the carbonyl group of α-keto acids to be protonated. However, the presence of proton causes not only the decomposition of a hydride species, which would act as a catalyst, but also formation of the α-hydroxy carboxylic acids as a byproduct by the competitive transfer hydrogenation of α-keto acids (eq 1).