Advances in the Synthesis of α-Methylenelactones

The synthesis of α-methylenelactones is a subject of continuing interest owing to the biological activity of natural products containing this structural unit. The present review summarizes the developments reported since the publication of previous reviews on this subject in 1975. Methods for the preparation of α-methylenelactones are classified into 2 groups: (1) construction of the α-methylenelactone ring from acyclic precursors bearing all necessary functional groups and (2) introduction of an α-CH₂-X group on to a preformed lactone ring and subsequent removal of the group X to give the methylene functionality. 1. Introduction 2. Construction of the α-Methylenelactone Unit from an Acyclic Precursor Bearing All Necessary Functionalities 2.1. Lactonization of α-Methylene γ,δ-unsaturated Acids or Esters 2.2. Cyclization of Substituted Acrylates 2.3. Oxidative Cyclization of 2-Methylene-1,4-diols 2.4. Addition of Ester Dienolates to Aldehydes 2.5. Reaction of α-Acrylate Cation Equivalents with Ketone Enolates 2.6. Cyclocarbonylation Reactions 2.7. Palladium-Catalyzed Cyclization of Homoallylic Carbonochloridates 2.8. Miscellaneous Reactions 3. α-Methylenation of Preformed γ-Butyrolactone Rings 3.1. Introduction of an α-CH₂-X Unit on to a Lactone Ring 3.2. Organoselenium Reagents as Precursors of the Double Bond