The synthesis of γ-alkylidenebutenolides

alpha,beta -Unsaturated gamma -lactones with an alkylidene subsititeut in the 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-harvesting in the ocean. A distinct sub-class within the gamma -alkylidenebutenolides consists of the pulvinones and pulvinic acids, which are dyes found in mushrooms. A structural feature shared by all gamma -alkylidenebutenolides, 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 thermodynamic advantage of the Z- vs. E-configuration is often quite small. Section I is devoted to the introduction. Section II starts with the landmark 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 -alkylidenebutenolides or, depending on the choice of the precursor, their E-isomers, follow as Section III. Section IV covers the metallocyclization/protonolysis approach to such compounds. Section V concerns a condensation strategy leading to gamma -alkylidenebutenolides from methylene-active compounds and derivatives of oxalic acid. Section VI deals with a Horner-Wadsworth-Emmons synthesis of two gamma -alkylidenebutenolides starting from selectively enolized 1,2-diketones. Section VII is devoted to methods leading to gamma -arylidene-alpha -aryl-beta -hydroxybutenolides ("pulvinones"). The synthetic chemistry of pulvinone-based carboxylic acids ("pulvinic acids") follows in Sections VIII and IX focusing on condensation and rearrangement routes, respectively. In order to facilitate comparison, comprehension, and analysis, most syntheses are traced back to commercially available starting materials, and pertinent reaction details are included in the footnotes of the Schemes.