Total synthesis of prostaglandin-F2α involving stereocontrolled and photo-induced reactions of bicyclo[3.2.0]heptanones

Abstract

A short total synthesis of prostaglandin-F_2α from cyclopentadiene is described. Acetalisation of bicyclo[3.2.0]hept-2-en-6-one (1) followed by formation of a single bromohydrin gave on treatment with base the epoxyacetal (4). Reaction of (4) with the appropriate organocuprate reagent introduced both the 12β side-chain and 11α-hydroxy-group of the embryonic prostaglandin. The fused cyclobutane ring is important as it controls both the stereoselectivity of epoxide formation and the regioselectivity of the subsequent ring-opening reaction. Furthermore, the unusual photochemical behaviour of cyclobutanones was exploited in this synthesis. Irradiation of the bicyclo[3.2.0]heptan-6-one (9) in aqueous solution and subsequent Wittig olefination afforded prostaglandin-F_2α Baeyer–Villiger oxidation of the same ketone (9) furnished the lactone (16), a known precursor of prostaglandin-E.