2-Bromoamides. Stereocontrolled substitution and application to the synthesis of compounds of biological interest

Abstract

2-Bromoamides are interesting and versatile intermediates for substitution of bromine by a variety of nucleophiles and for other synthetic approaches. Whereas emphasis is given to chiral 2-bromoamides, congeners carrying a tertiary or primary C-Br function have also been investigated. Among the peculiar features of 2-bromoamides there are the following: i) possibility of substitution at the tertiary C-Br (RCO2H, RR'NH, or a saccharide, as the nucleophiles); ii) chiral stability and stereochemical control at the secondary C-Br atom (RR'NH, ROH or a saccharide as the nucleophiles); iii) the presence of bromine allows cyclic voltammetry and electroreduction at controlled potential both of starting compounds and relevant intermediates; iv) the Cα polarity can be reversed upon electroreduction, and the resulting Cα enolate forms a C-C bond (CO2 as the electrophile). Application of the bromine substitution reaction allows the synthesis of aminoamides, alkoxyamides of simple alcohols and sugars, depsipeptides and ψ (NH) pseudopeptides, C2 symmetric compounds. © 1995, Elsevier B.V.