A Rhodium-Catalyzed Cyclization of Sulfonimidamides and Sulfondiimidamides: Synthesis and Exploration of Chiral Aromatic Heterocycles.

Although cyclic SIAs have demonstrated promising medicinal potential, methodologies for their construction remain relatively scarce. SIAs have proven to be suitable nitrene precursors for aziridination and C-H amination, when mixed with hypervalent iodine and a metal catalyst. Herein, we report the intramolecular cyclization of SIAs featuring N-acyl-type substitution via a dirhodium nitrene intermediate, forming a new N-heteroatom bond. The reaction leads to a diverse array of aromatic heterocyclic products featuring stereogenic sulfur centers. A combination of computational and spectroscopic techniques were utilized to investigate the complex relationship between stereochemistry and aromaticity as well as to explore their unique electronic and geometric features. Finally, the potential for these heterocyclic motifs to be utilized for medicinal chemistry was evaluated by synthesizing an analogue of enzalutamide featuring the heterocyclic core and determining its resulting pharmacokinetic properties and bioactivity.