Synthesis of Polysubstituted Tetrahydro‐1,4‐Thiazepines by Rhodium‐Catalyzed Ring Expansion of Dihydro‐1,3‐Thiazines with Diazoesters

We report a rhodium(II)‐catalyzed ring expansion of dihydro‐1,3‐thiazines with diazomalonates that provides tetrahydro‐1,4‐thiazepines bearing multiple stereocenters. The reaction proceeds through nucleophilic addition of the thiazine to the metallocarbene, catalyst release to form a sulfonium ylide, and rearrangement via an addition–elimination sequence to afford the thiazepine. A pronounced stereochemical effect arises for some cycloalkane‐fused thiazines: cis isomers efficiently furnish the corresponding cis ‐thiazepines, whereas trans isomers remain unreactive under standard conditions and react only at higher temperatures. Control experiments and density functional theory studies show that trans isomers coordinate more strongly to rhodium, thereby inhibiting the catalytic cycle. The synthetic versatility of the 1,4‐thiazepine scaffold is demonstrated by post‐transformations of the cyclic imine, including hydrolysis, reduction, and Krapcho decarboxylation.