Synthesis of Sulfoximine Propargyl Carbamates under Improved Conditions for Rhodium Catalyzed Carbamate Transfer to Sulfoxides

Sulfoximines provide aza-analogues of sulfones, with potentially improved properties for medicinal chemistry. The sulfoximine nitrogen also provides an additional vector for the inclusion of other functionality, Here, we report improved conditions for rhodium catalyzed synthesis of sulfoximine (and sulfilimine) carbamates, especially for previously low-yielding carbamates containing pi-functionality. Notably we report the preparation of propargyl sulfoximine carbamates to provide an alkyne as a potential click handle, Using Rh-2 (esp)(2) as catalyst and a DOE optimization approach provided considerably increased yields.

Automated summary

Sulfoximines offer a new approach for improving medicinal chemistry with the addition of other functional groups in sulfonyl compounds. By optimizing conditions, successful synthesis of carbamates with previously low yields, especially those containing pi-functionality, was achieved, including the preparation of propargyl sulfoximine carbamates as potential click handles. Notably, using Rh-2 (esp)(2) as catalyst and a DOE optimization approach led to significantly increased yields.