Predictions of the nucleofugality of carbanionic leaving groups based upon NMR chemical shifts in the enantioselective synthesis of sulfoxides

Our sequential coupling of Grignard reagents with suitable sulfinyl compounds involving the displacement of carbanionic leaving groups is now a well established procedure1 for the synthesis of enantiopure sulfoxides. After our synthetic and mechanistic investigation on the straightforward synthesis of selected sulfinyl precursors through a highly enantioselective oxidation of the sulfides with hydroperoxide in the presence of a complex between titanium and hydrobenzoin, more than 40 enantiopure aryl benzyl sulfoxides are now easily available as starting materials.2 Thus, we decided to give a deep insight into the reaction of organometallic reagents with the enantiopure items of this chemical library. We found that the nucleofugality of the leaving groups, and the order in the sequence of substitution, can be tuned by choosing the aryl benzyl sulfoxide that bears appropriate substituents on both the phenyl groups. We report now that the nucleofugality of the carbanionic leaving groups can be predicted by comparing analogous NMR chemical shifts of signals of the starting sulfoxides. The agreement between the experimental results and the expectations will be briefly surveyed.