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Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Azirid.pdf (1.6 MB)

Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

submitted on 09.10.2019, 20:52 and posted on 15.10.2019, 09:25 by Jennifer Schomaker, Josephine Eshon, Kate A. Nicastri, Steven C. Schmid, William T. Raskopf, Ilia A. Guzei,, Israel Fernández
Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.


NIH 1R01GM132300-01


Email Address of Submitting Author


University of Wisconsin-Madison



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest.