A short stereodivergent synthesis of (R) and (S)-nicotine

Dawood, Rafid S.; Stockman, Robert A.

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.

Citation

Dawood, R. S., & Stockman, R. A. (2025). A short stereodivergent synthesis of (R) and (S)-nicotine. New Journal of Chemistry, 49(12), 4860-4863. https://doi.org/10.1039/D5NJ00366K

• Journal Article Type: Article
• Acceptance Date: Feb 20, 2025
• Online Publication Date: Feb 21, 2025
• Publication Date: Mar 28, 2025
• Deposit Date: Mar 5, 2025
• Journal: New Journal of Chemistry
• Print ISSN: 1144-0546
• Electronic ISSN: 1369-9261
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 49
• Issue: 12
• Pages: 4860-4863
• DOI: https://doi.org/10.1039/D5NJ00366K
• Public URL: https://nottingham-repository.worktribe.com/output/45991439
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2025/nj/d5nj00366k