The synthesis of gamma-alkylidenebutenolides

alpha,beta -Unsaturated gamma -lactones with an alkylidene subsititeut in t he gamma -position ("gamma -alkylidenebutenolides") are well-known natural products. They vary in complexity from ("gamma -methylenebutenolide, which is an antibiotic; to peridinin, which is an important pigment for light-har vesting in the ocean. A distinct sub-class within the gamma -alkylidenebute nolides consists of the pulvinones and pulvinic acids, which are dyes found in mushrooms. A structural feature shared by all gamma -alkylidenebutenoli des, except the simplest, is that the C-gamma=Coff-ring bond is stereogenic . Therefore, in synthesis, this bond must be established stereoselectively. This is usually done in kinetically controlled reactions because the therm odynamic advantage of the Z- vs. E-configuration is often quite small. Section I is devoted to the introduction. Section II starts with the landma rk syntheses of the carotenoid gamma -alkylidenebutenolides peridinine and pyrrhoxanthine by Ito et al. beta -Elimination pathways from gamma-(alpha - heteroalkyl)-substituted butenolides giving Z-configured gamma -alkylideneb utenolides or, depending on the choice of the precursor, their E-isomers, f ollow as Section III. Section IV covers the metallocyclization/protonolysis approach to such compounds. Section V concerns a condensation strategy lea ding to gamma -alkylidenebutenolides from methylene-active compounds and de rivatives of oxalic acid. Section VI deals with a Horner-Wadsworth-Emmons s ynthesis of two gamma -alkylidenebutenolides starting from selectively enol ized 1,2-diketones. Section VII is devoted to methods leading to gamma -ary lidene-alpha -aryl-beta -hydroxybutenolides ("pulvinones"). The synthetic c hemistry of pulvinone-based carboxylic acids ("pulvinic acids") follows in Sections VIII and IX focusing on condensation and rearrangement routes, res pectively. In order to facilitate comparison, comprehension, and analysis, most synthe ses are traced back to commercially available starting materials, and perti nent reaction details are included in the footnotes of the Schemes.