Synthesis of C-4 substituted nicotine derivatives via an N-acylpyridinium salt of (S)-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-(dimethylphenyisilyl)nicotine was prepared and oxidized to afford (S)-4-hydroxynicotine.