Re-Evaluation of Product Outcomes in the Rh-Catalyzed Ring Expansion of Aziridines with N‑Sulfonyl-1,2,3-Triazoles

• Published in: Journal of organic chemistry Vol. 87; no. 16; pp. 10902 - 10907
• Main Authors: Dequina, Hillary J., Eshon, Josephine, Schmid, Steven C., Raskopf, William T., Sanders, Kyana M., Fernández, Israel, Schomaker, Jennifer M.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 19-08-2022
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c01186

N-heterocycles are prevalent in pharmaceuticals and natural products, but traditional methods often do not introduce significant stereochemical complexity into the ring. We previously reported a Rh-catalyzed ring expansion of aziridines and N-sulfonyl-1,2,3-triazoles to furnish dehydropiperazines with excellent diastereocontrol. However, later studies employing ketone-containing carbene precursors showed that [3,9]-bicyclic aziridine formation competes with production of the desired heterocyclic scaffolds. In light of these surprising results, our initial findings were re-examined both experimentally and computationally to reveal how noncovalent interactions and restricted bond rotation in the aziridinium ylide intermediate promote this unexpected reaction pathway.