Ionic Bicyclobutane as an Intermediate in the Reaction of PhS^-with 3-Halobicyclobutanecarbonitrile: Comparison between Thio^-and Oxycarbenium Ions

The nucleophilic reaction of phs^-with 3-chloro- and 3-bromobicyclobutanecarbonitrile (2-Cl (Br)) in MeOH and DME was investigated. The products in MeOH are the dithioketal 3 and the two cis-trans isomers of the thiooxoketal 4. The identity of the element (Cl or Br) in 2 strongly affects the product ratio 3/4 but has no effect on the stereodistribution of the two isomers of 4. It is shown that the mechanism of the reaction of phs^-with 2 in MeOH is similar to that of an alkoxide reacting with the same substrate (path c, Scheme I). After the cleavage of the central bond by the nucleophile, the thio halo ether group on C-3 expels a halide anion to form thiocarbenium before the negatively charged carbon reacts further. Addition of MeOH or PhSH to the zwitterionic intermediate completes the reaction. In DME, the mechanism is altered and 3-(phenylthio)bicyclobutanecarbonitrile (2-SPh) is obtained (path a, Scheme I). By carrying out the reaction at varying concentrations of MeOH in DME it is shown that 2-SPh is not obtained via a collapse of a zwitterionic intermediate but rather by a γ-elimination step (Scheme II). The γ-elimination mechanism prevails as long as the MeOH concentration in DME is kept below 2 M. Beyond this limit the change in medium polarity induces a gradual changeover in the mechanism and the proportion of the mixed ketal 4 is increased with the concentration of MeOH and follows a sigmoidic curve. A similar sigmoidic curve is obtained for the solubility of KBr in these solvent mixtures, supporting the assumption that the mechanistic changeover is caused by the change in the nature of the medium. Qualitative analysis shows that oxygen is superior to sulfur in enhancing the formation of an adjacent positive center.