Highly stereoselective synthesis of spiro-α-methylene-γ-butyrolactones: the role of α-hydroxy substitution

α-Methylene-γ-butyrolactones attenuate Staphylococcus aureus virulence by inhibition of transcriptional regulation

“…41 A Reformatsky reaction with ethyl 2-(bromo-methyl)acrylate yielded the nal aliphatic substituted lactone probes 1 and 2 as racemic mixtures. 42 In the case of phenyl substituted lactones, a Wittig reaction of benzaldehyde with (carbethoxyethylidene) triphenylphosphorane led to the formation of compound 14 which was brominated at its allylic position by using NBS and AIBN to yield lactone precursor 15. 43 The nal phenyl substituted lactones Fig.…”

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

“…Trivedi and co-workers employed it in a highly stereoselective synthesis of steroid-derived spiro-a-methylene-g-butyrolactones (Scheme 30). [98] A range of steroidal ahydroxyketones were utilized, and it was established that the a-hydroxy group was fundamental for the stereoselectivity, as the reaction proceeded via a transition state involving a chelate intermediate in which zinc is coordinated to both the hydroxy and carbonyl oxygen atoms. As an example, ahydroxyketone 147 gave the spiro-a-methylene-g-butyrolactone 148 in 76 % yield as a single diastereomer.…”

Natural and Synthetic Spirobutenolides and Spirobutyrolactones

“…Thereafter, ethyl 2-(bromomethyl) acrylate had been added and the reaction mixture was stirred for another 15 h at 37°C After this, 10% HCl was added and the resulting mixture was filtered, extracted and column purified to furnish desired compounds. [84] Similarly, a coupling reaction of β-propiolactone and cycloalkanone catalyzed by SmI 2 in THF at room temperature yielded 5-cycloalkyl-γ-butyrolactone (Scheme 32). [85] Another synthesis of tricyclic spirolactone has been performed using the Reformatsky reaction which involves bicyclic compounds as a substrate.…”

“…However, a steroid with α ‐hydroxy group delivered a single diastereomer in improved yields (Scheme ).In this protocol, under an inert atmosphere, a solution of steroidal ketone in THF was reacted with Zn dust for 15 minutes. Thereafter, ethyl 2‐(bromomethyl)acrylate had been added and the reaction mixture was stirred for another 15 h at 37 ° C After this, 10% HCl was added and the resulting mixture was filtered, extracted and column purified to furnish desired compounds …”