Abstract

The mechanism is investigated for Pd(0)-catalyzed spirocyclopropanation of π-allylpalladium 1,4-dipole with gem-difluoroalkene and 1,4-addition-induced dearomatization of 5-alkenylthiazolone with 2-bromomalonate. The π-allylpalladium 1,4-zwitterionic species was afforded by oxidative addition and rate-limiting decarboxylation. Then nucleophilic addition of anionic oxygen to gem-difluorinated carbon generated zwitterionic intermediate with dual Pd-π coordination. The intramolecular spirocyclization underwent through attack of anionic carbon to central carbon of π-allylpalladium giving palladacyclobutane, the reductive elimination of which yielded oxa/azaspiro [2.4]-heptane and Pd(0). The carbonyl of 5-alkenylthiazolone was activated by quaternary ammonium with enhanced electrophilicity of C-C double bond, which was attacked by carbanion of deprotonated bromomalonate in Michael 1,4-addition forming aromatized enolate. Subsequently, the rate-limiting intramolecular S_N2 nucleophilic substitution took place affording dearomatized ring closure product spirocyclopropylthiazole. The positive solvation effect is suggested by decreased absolute and activation energies in solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.

Keywords:Spirocyclopropanation; 1,4-addition; Dearomatization; 5-alkenylthiazolone; π-allylpalladium 1,4-dipole