A Short Stereodivergent Synthesis of (R) and (S)-Nicotine

Abstract

A straightforward and efficient enantioselective synthesis of (S)-nicotine and unnatural (R)-nicotine with high yields is presented. Judicious choice of solvent in the key asymmetric addition of the pyridyl Grignard reagent to the chiral sulfinimine promotes either an open or closed transition state, allowing the selective formation of either of two distinct diastereomers, which are then transformed into either enantiomer of the natural product via ring-closure and deprotection/methylation of the pyrrolidine amine.