Iminium salts cathodic reduction

Another methods for the electrochemical formation of the active carbanion is the cathodic reduction of iminium salts. When an iminium salt is reduced in the presence of a suitable alkylating agent, an alkyl group is introduced to the carbon atom of the imine. Some isoquinoline and indole type alkaloids are synthesized by using this substitution method as exemplified bellow by the synthesis of laudanosine 51 37>. 

The reduction of the iminium salt to an anionic species has been suggested to be the initiation step, since the best yield is obtained when the working potential of the cathode has a value inbetween the reduction peak potential of the iminium salt and that of the alkylating agent. 

The reaction was shown to be triggered by protonation of the ketone and reduction to 139. Cyclisation of the carbon centred radical to the pyridinium ring next produced radical cation 140. Addition of a second electron then gave enamine 141, which underwent reversible protonation to iminium salt 138. Further cathodic reduction completes the sequence (Scheme 38). Interestingly, such cyclisations appear to be reversible as the product mixtures attained better reflect a reaction under thermodynamic control than one under kinetic control <03EJO2919>. 

The reductive couphng of imines can follow different pathways, depending on the nature of the one-electron reducing agent (cathode, metal, low-valent metal salt), the presence of a protic or electrophihc reagent, and the experimental conditions (Scheme 2). Starting from the imine 7, the one-electron reduction is facihtated by the preliminary formation of the iminiiim ion 8 by protonation or reaction with an electrophile, e.g., trimethylsilyl (TMS) chloride. Alternatively, the radical anion 9 is first formed by direct reduction of the imine 7, followed by protonation or reaction with the electrophile, so giving the same intermediate a-amino radical 10. The 1,2-diamine 11 can be formed from the radical 10 by dimerization (and subsequent removal of the electrophile) or addition to the iminium ion 8, followed by one-electron reduction of the so formed aminyl radical. In certain cases/conditions the radical 9 can be further reduced to the carbanion 12, which then attacks the... 

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