Route to prostaglandins via a general synthesis of 4-hydroxycyclopentenones

The Piancatelli Rearrangement: New Applications for an Intriguing Reaction

“…This transformation had already been described by Stork et al, who treated 2 with chloral in the presence of triethylamine [26]. Piancatelli et al, also observed this migration during the chromatographic purification of 2 on neutral (for 2a) or basic alumina (for 2b-c) [27].…”

“…Some of the products arising from the application of this domino sequence are: 3E,5Z-misoprostol (21) [30], enisoprost (22) [31], 4-fluoro-enisoprost [32], 2-normisoprostol [33], prostaglandin E 1 (23) [34], ent-phytoprostane E 1 (24) and 16-epi-phytoprostane E 1 [35], bimatoprost (25,Lumigan™) and travoprost (26,Travatan™) [36,37] (Figure 1). Bimatoprost (25) and travoprost (26) can be synthesized from the common intermediate 4-silyloxycyclopentenone 28, whose production was set-up on a kg-scale by exploiting a "Piancatelli rearrangement/chloral-mediated isomerization" sequence, starting from furfural, and subsequent enzymatic resolution of the resulting 4-hydroxycyclopentenone 27 [38] The rearrangement of 2-furylcarbinols has also been applied to the total synthesis of natural products [41,42].…”

Studies towards dynamic kinetic resolution of 4-hydroxy-2-methylcyclopent-2-en-1-one and its E - O -trityloxime

“…The relevant intramolecular Michael-type hydroxy group participacion has been postulated to explain some properties of the parent hydroxy-ketone. 18 The corresponding optically active oximes (S)-E-and (S)-Z-9 were prepared starting from (S)-5 (98% ee). The resolution of rac-E-9 in solvents suitable for the racemization experiments with catalyst 4: toluene, chlorobenzene and dichloroethane at 40 ºC were examined.…”

Rapid Synthesis of Fused Oxabicycles through the Molecular Rearrangement of Spirocyclic Ethers

“…[4b] The migration of the alcohol functional group can occur in an intramolecular fashion (Figure 2, a) [7] or through a hydration-dehydration sequence (Figure 2, b). [8] Wu and coworkers recently took advantage of a two-step sequence, nucleophilic addition of a tethered alcohol followed by elimination of water, to gain access to fused oxabicycles from the corresponding 4-hydroxycyclopentenones (Figure 2, c). [9] We sought to develop a new strategy that would proceed through the spirocyclic ether and upon combination with our previous methodology would offer straightforward access to two classes of oxabicycles from the same furylcarbinol starting material.…”