SmI2-mediated hetero-coupling reaction of lactams with aldehydes; synthesis of indolizidine alkaloids, (−)-δ-coniceine, (+)-5-epiindolizidine 167B and (+)-lentiginosine

Treatment of alicyclic and aromatic lactams with several aldehydes in the presence of samarium(II) diiodide was found to undergo a novel nitrogen–carbon (hetero) coupling reaction to generate N-α-hydroxyalkylated lactams in high yield. The chiral lactams with an aldehyde-side chain incorporating the l-pyroglutamic acid- or l-tartaric acid-derived skeleton also reacted intramolecularly under the same conditions to afford the corresponding bicyclic coupling products, which were further applied to the convenient syntheses of (−)-δ-coniceine, (+)-5-epiindolizidine 167B and (+)-lentiginosine, respectively.