Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent

An increased interest to expand the three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared to their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) center to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange (SuFEx) chemistry has enabled the development of an enantiopure bifunctional S(VI) transfer reagent (t-BuSF) to overcome current synthetic limitations. Here, this reagent platform serves as a chiral SuFEx template for the rapid asymmetric synthesis of over seventy different sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiopurity and good overall yields. Furthermore, the practical utility of t-BuSF was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogs.