Synthesis of novel trifluoromethylated beta-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 beta -acetal-gem-dio ls, 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 diols (6a = methoxy, 6b = ethoxy, 6c = all yloxy, 6d = ynyloxy) from the reaction of 4-ethoxy-1,1,1-trifluoro-3-buten- 2-one (1) and 1-(4,5-dihydrofuran-3-yl)-2,2,2-trifluoro-ethanone (2) with s odium azide in hydro-alcoholic medium, is presented. From these reactions, a small amount (ca. of 20%) of the parent trifluoromethylated beta -acetal- ketones, 4-alkoxy-4-ethoxy-1,1,1 -trifluoro-butan-2-ones (3a-d) and 2,2,2-t rifluorol-(2-alkoxy-tetrahydro-furan-3-yl)-ethanones (5a-d) were also obtai ned. The synthetic potential of the trifluoromethylated P-acetal-diols was demonstrated by its application to the synthesis of 3-ethoxy-5-hydroxy-5-tr ifluoromethyl-pyrrolidin-2-one (7). (C) 2001 Elsevier Science B.V. All righ ts reserved.