The 1,4-addition of 2-, and 4-pyridyl cuprates to enones, enoates and unsaturated nitriles have been shown for the first time to be synthetically useful, obtaining the 1,4-addition products in high yields. This methodology has enabled an expedient, highly diastereo- and enantioselective synthesis of (-)-evoninic acid (4), using a lipase mediated hydrolytic kinetic resolution step to control the absolute stereochemistry. Model studies made towards the synthesis of hydroxyiso-evoninic acid have established the synthesis of the un-natural product hydroxy evoninic acid 178.
The synthesis of hydroxy iso-evoninic acid using a strategy analogous to that used for the synthesis of hydroxy evoninic acid was also investigated. Unfortunately, installation of the methyl group a to the ester in substrate 189 through a variety of methods proved to be impossible.