Keto‐Enol Tautomerization Controls the Acid‐Catalyzed Robinson Annulation ‐ A DFT Study

Abstract

AbstractThree Robinson annulation reactions (A), (B) and (C) were investigated by DFT calculations. (A) is a base catalyzed one, where cyclohexanone, methyl vinyl ketone (MVK) and OH−(H2O)7 were employed as reactants. Eight elementary steps were obtained. The second transition state, TS2(A), is of the Michael addition prompted by the secondary orbital interaction, and TS5(A) is of the aldol condensation. The second TS of E1cB, TS8(A), has an appreciable activation energy, which would make the diketone A‐4 and ketol A‐7 detectable species. (B) is an acid catalyzed reaction, where 2‐methylcyclohexanone, MVK and H3O+(H2O)7 were adopted as reactants. Seven elementary steps were obtained. All the intermediates in B‐2 to B‐7 are neutral species (not protonated). The keto‐enol tautomerization assisted by the proton transfer is involved in all TSs. (C) is a neutral reaction, where 2‐methylcyclopentane‐1,3‐dione, 1‐chloro‐3‐pentanone and (H2O)8 were reactants. The first C−C bond formation is brought about by the nucleophilic substitution (SN2) where the leaving group is the chloride ion. The concomitantly generated H3O+ works as the acid catalyst to promote the subsequent processes. Again, the keto‐enol tautomerization is involved in all TSs.