Fluorinated butanolides and butenolides: Part 8. 2-(Trifluoromethyl)butan-4-olides by synthesis from methyl 3,3,3-trifluoropyruvate as building block

2-Hydroxy-2-trifluoromethylbutan-4-olides (8–10) were prepared by a four step synthesis starting from a ketone and methyl 3,3,3-trifluoropyruvate (1) as a building block. Uncatalyzed chemospecific aldolization of ketones with 1 afforded 2 hydroxy-4-oxoesters 2–4 that were selectively reduced at the oxo group by sodium borohydride to the corresponding 2,4-dihydroxyesters 5–7. Acid-catalyzed cyclization of dihydroxysters 5–7 to lactones 8–10 was strongly dependent on their structure. The lactone-ring closure with the hydroxy group at the hydroxylated cyclopentane ring afforded bicyclic lactone (10) with cyclopentane cis-annulation. 2-Hydroxy-2 trifluoromethylbutanolides appeared to be highly resistent to dehydration or eliminations of the corresponding mesylates or triflates.