TMSCH2Li-induced regioselective lithiation of (S)-nicotine

Abstract

The first regioselective C-4 lithiation of (S)-nicotine has been realized using TMSCH₂Li as basic reagent in toluene. The reaction proceeded under mild conditions with a small excess of electrophile. The 4-chloro derivative was subsequently metallated at C-5 with the same basic reagent in THF at −78 °C. This methodology opens a straightforward access to functional diversity in (S)-nicotine chemistry.