Ring-Closing Metathesis Strategies to Cyclic Sulfamide Peptidomimetics

Ring-closing metathesis (RCM) strategies toward the synthesis of a number of constrained sulfamides are discussed. This approach exploits the inherent chemistry of sulfamides and sulfonyl carbamates to generate both symmetric and unsymmetric cyclic sulfamides. Two strategies are revealed, one centers on the RCM reaction of allylated sulfamides 9a–e to generate the C2-symmetric cyclic sulfamides 4a–e in high yields. A second RCM strategy utilizes the known sulfonyl carbamate 15 to prepare unsymmetric cyclic sulfamides 16 and 6 in two four-step sequences. Overall, the routes described are applicable to the synthesis of a variety of constrained dipeptidal sulfamides representing novel peptidomimetic scaffolds.