The sulfoximines and sulfonimidamides are functional groups that are obtained by replacing one of the oxygen atom of respectively sulfones and sulfonamides by a nitrogen atom. In reason of their 3D-shape, good aqueous solubility and high chemical and metabolic stability, these functional groups have recently received much attention from the medicinal chemists. Unfortunately, synthesizing these structures remains challenging because of the existing non-friendly-user protocols using either for example thiols or gaseous SF4.
The Willis group and his industrial collaborators at UCB developed a unified one-pot synthesis of sulfoximines and sulfonimidamides by harnessing sulfinyl nitrenes. Practically, they developed a novel sulfinylhydroxylamine reactant that upon reaction with a carbon-centered organometallic nucleophile gives a sulfinyl nitrene species. This intermediate then reacts with another organometallic species to give a sulfoximine or with an amine to yield a sulfonimidamide. Overall, this one-pot process takes less than 20 min with an ample scope. To gain more insight into the mechanism of this very interesting transformation, a computational investigation using density functional theory was also undertaken.