Stability of Prostacyclin Analogues: An Unusual Lack of Reactivity in Acid-Catalyzed Alkene Hydration

Abstract
Prostacyclin analogue 5 undergoes specific acid-catalyzed hydration (kH+ = 1.9 × 10−7M−l sec−1 at 25°C) and a pH-independent oxidation reaction (k0 = 1.2 × 10−10 sec−1 at 25°C) above pH∼5. The hydration reaction for 5 is much slower than for other structurally similar exocyclic alkenes, even though the rate-determining step is proton transfer. This slowness of reaction and an analysis of the pH–rate profile show that 5 does not exhibit significant intramolecular general acid catalysis, as does prostacyclin.