A totally stereoselective total synthesis of epi-lupinine (1) has been developed that starts with methyl sórbate (6). Alkylation of 6 with bromide 8 gave diene 10, which was elaborated into the imino Diels-Alder precursor 17. Thermolysis of 17 provided exclusively bicyclic lactam 18. Acyl imine 4 (R = CH2Ph) has been postulated as an intermediate in this cycloaddition. The stereoselectivity of the reaction is rationalized on the basis of a transition state, 22, which has (1) a planar, s-cis acyl imine moiety, (2) a carbonyl group endo to the diene, and (3) a quasi-boat bridging-chain conformation. Reduction of 18 afforded racemic epi-lupinine. Cryptopleurine (2) was prepared by starting from the readily available phenanthrene aldehyde 33. Cyclization of methylol acetate 37 gave lactam 38. It was demonstrated that only the E form of 37 cyclizes via (E)-acyl imine 39. The Z isomer 40 did not lead to a Diels-Alder product. Hydride reduction of lactam 38 gave racemic cryptopleurine.
All Science Journal Classification (ASJC) codes
- Organic Chemistry