Anodic Cyanation of (S)-(-)-1-(1-Phenylethyl)piperidine: an Expeditious Synthesis of (S)-(+)-Coniine

Abstract

A short and efficient asymmetric synthesis of enantiopure (S)-(+)-coniine is reported. Anodic cyanation of (-)-1-[(1S)-1-phenylethyl]piperidine, derived from [(1S)-1-phenylethyl]amine, results in regioselective formation of the corresponding α-amino­nitrile, which was alkylated with propyl iodide to give a bifunc­tional derivative. The latter underwent a stereoselective reductive decyanation (80% de), the product of which was hydrogenolyzed to afforded (S)-(+)-coniine (99% ee) with an overall 35% yield from (-)-1-[(1S)-1-phenylethyl]piperidine.

Key words

alkaloids - anodic cyanation - alkylation - metallation - stereoselective synthesis

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17

Aminonitrile 3 readily decomposed on TLC plate, R _f value is given for guidance.