Synthesis of γ,γ-difluoro-β-hydroxy-δ-lactones as new precursors of HMG-CoA reductase inhibitor

A series of γ,γ-difluoro-β-hydroxy-δ-lactones 1 were efficiently synthesized as new precursors of HMG-CoA reductase inhibitor in one pot by treatment of readily prepared gem-difluoromethylenated acetonides 3 with trifluoroacetic acid. Contrarily, acetonides 3 could be transformed to the γ,γ-gem-difluoromethylenated α,β-unsaturated δ-lactones 2 through hydrolyzation and lactonization in refluxing toluene.

Graphical abstractA series of γ,γ-difluoro-β-hydroxy-δ-lactones 1 was efficiently synthesized as new precursors of HMG-CoA reductase inhibitor in one pot by treatment of readily prepared gem-difluoromethylenated acetonides 3 with trifluoroacetic acid. Contrarily, acetonides 3 could be transformed to the γ,γ-gem-difluoromethylenated α,β-unsaturated δ-lactones 2 through hydrolyzation and lactonization in refluxing toluene.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► CF2 group was first introduced to β-hydroxy δ-lactones at the γ-position. ► β-Hydroxy δ-lactones were synthesized as HMG-CoA reductase inhibitor precursors. ► Acetonides underwent cyclization to afford β-hydroxy δ-lactones promoted by TFA. ► Acetonides were transferred to α,β-unsaturated δ-lactones in refluxing toluene.