Synthesis of Functionalized Alpha-methylene Lactones

Abstract

A recent report² prompts us to disclose our progress pertaining to the synthesis of α-methylene- δ-valerolactones fused onto an unsaturated functionalized ring 1. As part of our work in this area,^3,4 we desired to obtain a sample of lactone 4 for further elaboration. Thus, alkylation of 1,3-cyclohexanedione with α-(l-bromomethyl)acrylate⁵ yielded compound 2 which was subsequently hydrolyzed to the corresponding acid 3. Initial attempts to cyclize compound 3 by heating in trifluoroacetic anhydride or acetic anhydride resulted in the formation of the desired lactone 4 along with a substantial amount of another compound 5. When lactone 4 was allowed to sit at room temperature or was heated in the presence of acid, it was transformed into compound 5. On the basis of the available data, structure 5 is proposed for this compound.⁶ The protected form⁷ of lactone 4 was eventually obtained by reacting acid 3 with dicyclohexylcarbodiimide in pvridine⁸ followed by treatment with thiophenol in pyridine.