Copper-Catalyzed Chan-Lam Coupling of NH-Diaryl Sulfondiimines

Sulfondiimines, which contain a tetrasubstituted sulfur centre bearing two nitrogens and two carbon substituents, are a class of underexplored scaffolds in organic chemistry. Fascinated by some unique yet intriguing properties, sulfondiimines appear as leads in discovery industry, but the lack of efficient synthetic approaches holds back their further uptake by medicinal chemistry. Herein, a general and practical copper-catalyzed Chan-Lam coupling of NH-diaryl sulfondiimines with arylboronic acids is presented. A simple copper catalyst efficiently facilitated the highly chemoselective construction of C-N bond, allowing the preparation of a variety of N-arylated diaryl sulfondiimines in good yields under mild and environmentally benign conditions. An array of protecting groups on imine moieties were well tolerated, offering diversified accesses to NH,NAr-diaryl sulfondiimines, a class of versatile building blocks. Moreover, an aza-analogue of an EphB4 inhibitor featuring a sulfondiimine-based pharmacophore was generated employing our Chan-Lam coupling as the key step.

Automated summary

Sulfondiimines, an underexplored scaffold in organic chemistry, have been synthesized efficiently through a copper-catalyzed method presented in this study. The synthesis allows the preparation of diversified sulfondiimines with various functional groups, and it was also used to generate an aza-analogue of an EphB4 inhibitor featuring a sulfondiimine-based pharmacophore.