A novel reductive aminocyclization for the syntheses of chiral pyrrolidines: Stereoselective syntheses of (S)-nornicotine and 2-(2'-pyrrolidyl)-pyridines

(S)-Nornicotine 2 was synthesized in four steps. A key step in the synthesis involved reductive aminocyclization of a 1,4-ketoaldehyde with 2,3,4,6-tetra-O-pivaloyl-β-D-galactosylamine 1 in the presence of sodium cyanoborohydride, diastereoselectively affording the corresponding stereoisomer 6 in 45% yield. The aminosugar moiety could be easily removed by acidic hydrolysis to furnish 2. The aminocyclization was further extended to asymmetric syntheses of novel chiral 2-(2'-pyrrolidyl)-pyridine ligands 12 and 13.