Rates and mechanisms for the ring opening, ring closure and ring transformation reactions of the di-γ-lactone dihydrocanadensolide(DHC)

Abstract

The title di-γ-lactone 1 ring opens in alkali to the monolactones 2–4 by three parallel routes: via hydrolysis to 2 and 3 and viaβ-elimination to give 4. The last is probably an (E1cb)_I process, though there is conflicting evidence and the mechanism is uncertain. The two hydrolyses are much faster than models would predict owing essentially to the ΔS^‡ term, and an unusual intramolecular interaction which results from steric crowding is invoked. While further hydrolysis of the monolactone 3 is straightforward, that of 2 probably goes via the δ-lactone 8, whose rapid pre-equilibration with 2 has also been studied. This hydrolysis is characterised by a highly abnormal near-zero ΔS^‡ value which is tentatively explained as being due to exclusion of water from the transition state by intramolecular solvation. Rates for the reverse lactonisation process are unremarkable, but analysis of the activation parameters reveals evidence for ring strain in the formation of 1 which precisely balances the normal rate increase expected through approximation.