Allylic halogenation of unsaturated amino acids

Abstract

A range of dehydro amino acid derivatives has been prepared and subjected to halogenation using either molecular bromine or chlorine, or NBS. Allylic halogenation of the unsaturated amino acid side chains occurs through radical bromination with NBS. The procedure is complementary to treatment with chlorine, which also affords allyl halides. This latter and unusual reaction is shown through a deuterium labelling study to proceed via an ionic mechanism. The choice of NBS or chlorine for allyl halide synthesis is shown to depend on the potential to avoid competing reactions, such as halolactonization of leucine derivatives with chlorine, and hydrogen abstraction and bromine incorporation at multiple sites on treatment of isoleucine derivatives with NBS. The synthetic utility of the allyl halides prepared in this study is indicated through the synthesis of a cyclopropyl amino acid derivative and the extension of the carbon skeleton of an amino acid side chain.