Total Synthesis of Enantiopure Pyrrhoxanthin: Alternative Methods for the Stereoselective Preparation of 4‐Alkylidenebutenolides

A new stereocontrolled total synthesis of the configurationally labile C₃₇‐norcarotenoid pyrrhoxanthin in enantiopure form has been completed. A highly stereoselective Horner–Wadsworth–Emmons (HWE) condensation of a C₁₇‐allylphosphonate and a C₂₀‐aldehyde was used as the last conjunctive step. Both a Sonogashira reaction to form the C₁₇‐phosphonate and the final HWE condensation proved to be compatible with the sensitive C7–C10 enyne E configuration. Regioselective (5‐exo‐dig) silver‐promoted lactonization reactions of three alternative pent‐2‐en‐4‐ynoic acid precursors with increased complexity, including a fully functionalized C₂₀‐fragment, were explored for the preparation of the γ‐alkylidenebutenolide fragment. This survey extends the existing methodologies for the preparation of oxygen‐containing carotenoids (xanthophylls) and streamlines the synthesis of additional members of the C₃₇‐norcarotenoid butenolide family of natural products.