Mechanism of Ylide Transfer to ­Carbonyl Compounds: Density Functional Calculations

We report a computational study on the mechanism of the reaction of ethyl acetoacetate (1) with two sulfur reagents: Martin's sulfurane (Ra) and a mixture of diphenyl sulfide and triflic anhydride (Rb). These reagents are able to provide a sulfonium ion [Ph₂S-OX]⁺ and an anionic nucleophile ^–OX as active species [X = C(CF₃)₂Ph for Ra and X = SO₂CF₃ for Rb] in the reaction. Experimentally, the reaction of Ra with carbonyl compounds provides an S-ylide as the only product whereas a low yield of S-ylide is obtained in the case of Rb. To elucidate the mechanism of these reactions with prototype substrate 1, different plausible pathways have been investigated using density functional theory (DFT), mostly at the B3LYP-D/6-31+G** level. According to DFT calculations, initial deprotonation of 1 may furnish either an enolate (with Ra) or an O-sulfenylated enolate (with Rb). Subsequent nucleophilic addition of the enolate to the sulfonium ion provides the simplest route to S-ylide product, which is favored when using reagent Ra. In the case of reagent Rb, the preferentially formed O-sulfenylated enolate may undergo either a series of nucleophilic displacements or a [1,3] sigmatropic shift or a [3,3] sigmatropic rearrangement, all followed by a final deprotonation to yield the product. These conversions are highly exothermic and involve thermodynamically stable products. The [3,3] sigmatropic rearrangement that directly produces an arylated carbonyl compound is computed to be the kinetically most facile reaction with Rb. Overall, the computational results unveil detailed mechanistic scenarios detailing possible transformations and providing qualitative explanations for some of the experimental findings