jo010386b_si_001.pdf (427.49 kB)
Efficient Enantiomeric Synthesis of Pyrrolidine and Piperidine Alkaloids from Tobacco
journal contribution
posted on 2001-08-23, 00:00 authored by Felpin, Sandrine Girard, Giang Vo-Thanh, Richard J. Robins, Jean Villiéras, Jacques LebretonAn enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine
2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known
as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azido-but-3-enyl)-pyridine 15. An intramolecular hydroboration−cycloalkylation of the homoallylic azide
intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis
reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic
acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially
available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco
alkaloids is described: (S)-nornicotine 1 (5 steps, with an overall yield of 70%), (S)-nicotine 2 (6
steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine
5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).