Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

Abstract

The reactivities of cyclic enones and α,β-unsaturated lactones were characterized by following the kinetics of their reactions with colored carbon-centered reference nucleophiles in DMSO at 20 °C. The experimentally determined second-order rate constants k₂ were analyzed with the Mayr–Patz equation, lg k = s_N(N + E), to furnish the electrophilicity descriptors E for the Michael acceptors. Cyclic enones and lactones show different reactivity trends than their acyclic analogs. While cyclization reduces the reactivity of enones slightly, α,β-unsaturated lactones are significantly more reactive Michael acceptors than analogously substituted open-chain esters. The observed reactivity trends were rationalized through quantum-chemically calculated Gibbs energy profiles (at the SMD(DMSO)/M06-2X/6-31+G(d,p) level of theory) and distortion interaction analysis for the reactions of the cyclic Michael acceptors with a sulfonium ylide. The electrophilicities of simplified electrophilic fragments reflect the general reactivity pattern of structurally more complex terpene-derived cyclic enones and sesquiterpene lactones, such as parthenolide.