The one-step three-component reaction of an amine, an aldehyde, and an organoboronic acid is a practical and highly versatile synthetic process. This metal-free C-C bond forming reaction is atom economical, and has as its major by-product only boric acid, a small and non-toxic compound. Typically, this chemistry is performed in an organic solvent, and it is applicable to the synthesis of a wide range of multifunctional amines and amino acid derivatives. Herein, we describe an even more environmentally-friendly version of this multicomponent process, where the only solvent is water. For example, the metal-free, one-step reaction of the alanine-proline dipeptide (1) with glyoxylic acid (2), and styryl boronic acid (1), led to the synthesis of the corresponding iminodicarboxylic acid derivative (4). Hydrogenation of 4 in water led to the production of Enalaprilat (5), the active ingredient of the drug Enalapril (brand name Vasotec), which is a widely used medication for the treatment of high blood pressure, symptomatic heart failure, and kidney disease.

Boron-mediated metal-free multicomponent synthesis of amino acid derivatives in water

256th National Meeting (2018)

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