Studies On The Synthesis And Reduction Of α,β-Dehydroamino Acid Derivatives

Functionalized enamines have played a very important role in the drug design and synthesis of a variety of different structures which possess biological activities. As members of this family,α,β-dehydroamino acids andα-ketoenamines (also referred to asα,β-dehydroamino acid derivatives) occur as frequent frameworks in natural products and biologically active compounds. They can participate in various organic reactions and thus they are useful synthons in organic synthesis. In virtue of the wide application ofα,β-dehydroamino acids andα-ketoenamines in organic chemistry, there is still a need to develop facile and practical synthetic methods for their preparation.According to the process already reported in the literature, theα-bromo ketones and hydroxamates with various different substituents were prepared from inexpensive starting materials.Herein we disclose a mild and efficent one-pot synthetic strategy for the preparation ofα,β-dehydroamino acid derivatives through the reactions ofα-bromocarbonyl compounds with hydroxamates due to the easy cleavage of nitrogen-oxygen bond under basic conditions. A series of compounds with a single isomer were predominately generated via this method, and thus some rules of this reaction has been found out. The geometry of the products has been confirmed as Z-configuration based on single-crystal X-ray analysis, NOE experiment and a comparison with the previous literature.The reduction of carbon-carbon double bond ofα,β-dehydroamino acid derivatives was investigated. It was found that TMSCl/KI/MeCN was a simple, efficient, mild and inexpensive reductive system and it was used to reduceα,β-dehydroamino acid derivatives for the first time. Variousα,β-dehydroamino acid derivatives were reduced in excellent yields under this condition. The structures of these new compounds were confirmed by NMR spectra.