Synthesis of alkaloidal compounds using an electrochemical reaction as a key step

Abstract

This review describes application of electroorganic reactions to synthesis of some key skeletons which are commonly found in natural alkaloids and some key intermediates which are useful materials for formation of the alkaloidal structures. The methods of synthesis are classified into three categories, namely, (1) Oxidative coupling, (2) Oxidative activation of the position α to the nitrogen atom of amines and (3) Reductive addition and substitution. In the first category, inter- and intra-molecular couplings of phenols and phenolic ethers and their application to synthesis of morphinandienone type alkaloids are mainly described. The second category is devoted to the anodic activation and subsequent carbon-carbon bond forming reactions at the position α to the nitrogen atom of amines. A variety of nitrogen heterocycles including quinoline, pyrrolizidine, indolizidine and quinolizidine skeletons are synthesized by using this methodology. In the third category, formation of active species by cathodic reduction of alkyl or aryl halides and their addition to unsaturated systems such as aromatic nucleus and carbonyl groups are mentioned. Optically active pyrrolizidine and indolizidine skeletons are obtained by this method. Reductive formation of anionic active species is also achievable by cathodic reduction of iminium salts. The successful application of substitution reaction between this active species and benzyl halides to the synthesis of indole and isoquinoline alkaloids is also contained in the third category.