Synthesis of C-4 Substituted Nicotine Derivatives via an <i>N</i>-Acylpyridinium Salt of (<i>S</i>)-Nicotine

A variety of novel nicotine derivatives were prepared from (S)-nicotine via a two-step sequence. Addition of a cuprate reagent to an N-acylpyridinium salt of nicotine, followed by aromatization with elemental sulfur, afforded C-4 substituted nicotines in moderate to high yield. Using this method, 4-(dimethylphenylsilyl)nicotine was prepared and oxidized to afford (S)-4-hydroxynicotine.