Extremely high regio- and stereoselective C–C bond formation of substituted γ-hydroxylactams: synthesis of macronecines based on their structural duality

With a view to develop a new synthetic entry for the necine bases, treatment of functionalized γ-hydroxylactams was found to undergo quite high regio- and diastereoselective carbon–carbon bond formation reactions, affording the corresponding structurally dualistic alkylated lactams in satisfactory yields. The reaction was further applied to the practical and efficient synthesis of (±)-macronecine [(1S∗,2R∗,7aR∗)-1-hydroxymethyl-2-hydroxypyrrolizidine] and (±)-2-epi-macronecine [(1S∗,2S∗,7aR∗)-1-hydroxymethyl-2-hydroxypyrrolizidine].