Dimerization Strategies for the Synthesis of High-Order Securinega Alkaloids

We describe different modes of dimerization of various alpha',gamma-dioxyenone derivatives with potential applications to the synthesis of high-order securinega alkaloids. We learned that the relative stereochemical relationship between alpha'- and gamma-hydroxyl groups of the alpha',gamma-dihydroxyenone derivative determines the mode of dimerization. While cis-alpha',gamma-dioxyenone 26 provided the Rauhut-Currier-type (RC-type) dimer 31 upon reaction with TBAF, trans-alpha',gamma-dihydroxyenone 34 afforded dimeric tetrahydrofuran derivative 41 under the same reaction conditions. We also noticed that the protection of the gamma-hydroxyl group drastically changes the reaction outcomes. While cis-alpha'-oxy-gamma-OPiv-enone 49 did not show any reactivity in the presence of TBAF, trans-alpha'-hydroxy-gamma-OPiv-enone 45 produced the RC-type dimer 46 under the same reaction conditions. Computational analysis revealed the detailed mechanism of the latter transformation.