Efficient Enantiomeric Synthesis of Pyrrolidine and Piperidine Alkaloids from Tobacco Felpin GirardSandrine Vo-ThanhGiang RobinsRichard J. VilliérasJean LebretonJacques 2001 An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (<i>S</i>)-nornicotine <b>1</b>, (<i>S</i>)-nicotine <b>2</b>, (<i>S</i>)-anatabine <b>3</b>, (<i>S</i>)-<i>N</i>-methylanatabine <b>4</b>, (<i>S</i>)-anabasine <b>5</b>, and (<i>S</i>)-<i>N</i>-methylanabasine <b>6</b>, known as natural products in tobacco, was established from a common chiral homoallylic (<i>S</i>)-3-(1-azido-but-3-enyl)-pyridine <b>15</b>. An intramolecular hydroboration−cycloalkylation of the homoallylic azide intermediate <b>15</b> served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (<i>S</i>)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester<b> 20</b> served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde <b>13</b>, a short and convenient enantiomeric synthesis of tobacco alkaloids is described:  (<i>S</i>)-nornicotine <b>1</b> (5 steps, with an overall yield of 70%), (<i>S</i>)-nicotine <b>2</b> (6 steps, 65%), (<i>S</i>)-anatabine <b>3</b> (8 steps, 30%), (<i>S</i>)-<i>N</i>-methylanatabine <b>4 </b>(8 steps, 25%), (<i>S</i>)-anabasine <b>5</b> (8 steps, 35%), and (<i>S</i>)-<i>N</i>-methylanabasine <b>6</b> (8 steps, 25%).