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 [Ph 2 S‐OX] + and an anionic nucleophile – OX as active species [X = C(CF 3 ) 2 Ph for Ra and X = SO 2 CF 3 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.