The β-elimination route to stereodefined γ-alkylidenebutenolidesDedicated to Dr Klaus Brückner (retired from Cela-Merck, Ingelheim) on the occasion of his 75th birthday.

Abstract

γ-Alkylidenebutenolides are biologically significant compounds and comprise compounds as structurally and functionally diverse as the inhibitor dihydroxerulin (Z-61, Scheme 16) of cholesterol biosynthesis or the carotinoid peridinin (Z-18a, Scheme 5) which plays a dominant role in marine photosynthesis. For the stereo-controlled obtention of γ-alkylidenebutenolides Z-2 or E-2 with or without alkyl substituents at C-α or C-β, a general strategy has been developed (Scheme 1). The key step of this strategy is the stereospecific anti-elimination of water from diastereopure γ-(α-hydroxyalkyl)butenolides lk-1 or ul-1—be they racemic or enantiopure (lk = like, ul = unlike: γ-(α-hydroxyalkyl)butenolides lk-1 give γ-alkylidenebutenolides Z-2, while γ-(α-hydroxyalkyl)butenolides ul-1 furnish the isomeric γ-alkylidenebutenolides E-2. As dehydrating agents we used mixtures of triflic anhydride and pyridine or of diethyl azodicarboxylate and triphenylphosphine. Previous β-eliminations providing γ-alkylidenebutenolides exhibited in general little stereoselectivity and no stereospecifity at all (exception: Scheme 10), irrespective of whether this β-elimination was performed separately or took place in situ.