Synthesis of novel trifluoromethylated β-acetal-diols and their application to the synthesis of 3-ethoxy-5-hydroxy-5-trifluoromethyl-pyrrolidin-2-one

The synthesis of a series of novel trifluoromethylated β-acetal-gem-diols, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butane-2,2-diols (4a=methoxy, 4b=ethoxy, 4c=allyloxy, 4d=ynyloxy) and 1-(2-alkoxytetrahydro-furan-3-yl)-2,2,2-trifluoro-ethane-1,1-diols (6a=methoxy, 6b=ethoxy, 6c=allyloxy, 6d=ynyloxy) from the reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (1) and 1-(4,5-dihydro-furan-3-yl)-2,2,2-trifluoro-ethanone (2) with sodium azide in hydro-alcoholic medium, is presented. From these reactions, a small amount (ca. of 20%) of the parent trifluoromethylated β-acetal-ketones, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butan-2-ones (3a–d) and 2,2,2-trifluoro-1-(2-alkoxy-tetrahydro-furan-3-yl)-ethanones (5a–d) were also obtained. The synthetic potential of the trifluoromethylated β-acetal-diols was demonstrated by its application to the synthesis of 3-ethoxy-5-hydroxy-5-trifluoromethyl-pyrrolidin-2-one (7).