Ligand-controlled rhodium­(I)-catalyzed denitrogenative transformations of a range of 4-vinyl-1,2,3-thiadiazoles possessing electron-donating substituents at the C5-position of the heterocycle have been demonstrated. With [Rh­(COD)2]­BF4, vinylic 1,2,3-thiadiazoles undergo an intramolecular transannulation reaction to afford substituted furans. In contrast, the [Rh­(COD)­DPPF]­BF4 catalytic system inhibits the intramolecular reaction but promotes intermolecular transannulation with both electron-deficient and electron-rich terminal alkynes, providing access to densely functionalized thiophenes with unexpected regioselectivity. Experimental and computational mechanistic studies were performed to gain insights into the Rh­(I)-catalyzed intramolecular transannulation of vinylic 1,2,3-thiadiazoles, with a focus on understanding the influence of the C5-substituent on reactivity and the role of the DPPF ligand. Importantly, our crystallographic data uncovered that the true structure of the organorhodium intermediate involved in Rh­(I)-catalyzed denitrogenative reactions of 1,2,3-thiadiazoles is likely to be a four-membered cyclometalated Rh­(III) complex.

Despite the growing use of denitrogenative reactions of 1,2,3-thiadiazoles in heterocycle synthesis, the origin of the varied reactivity and divergent regioselectivity observed in their transannulation reactions is not well understood....

Simple and convenient methods for the synthesis of a range of new 1,2,3-thiadiazole derivatives, including ethyl esters, alcohols, and aldehydes, were developed. Moreover, twenty-nine new structurally diverse 4-vinyl-1,2,3-thiadiazoles were successfully synthesized in 18-89 % yield via Knoevenagel condensation. NOESY-experiments were performed for E/Z-assignment of isomeric mixtures. The structure of five of the new vinylic derivatives has been confirmed using X-ray diffraction analysis. Using the example of ethyl (E)-2-cyano-3-(5-(pyrrolidin-1-yl)-1,2,3-thiadiazol-4-yl)acrylate, the possibility of dimerization with the formation of diethyl(1R,2R,3S,4S)-1,3-dicyano-2,4-bis(5-(pyrrolidin-1-yl)-1,2,3-thiadiazol-4-yl)cyclobutane-1,3-dicarboxylate was demonstrated, allowing the first 1,2,3-thiadiazole substituted cyclobutane to be synthesized.