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.
Piperazines are prevalent in pharmaceuticals and natural products,
but traditional methods do not typically introduce stereochemical
complexity into the ring. To expand access to these scaffolds, we
report Rh-catalyzed ring expansions of aziridines and N-sulfonyl-1,2,3-triazoles to furnish dehydropiperazines with excellent
diastereocontrol. Productive ring expansion proceeds via a pseudo-1,4-sigmatropic
rearrangement of an aziridinium ylide species. However, the structural
features of the carbene precursor are important, as pyridotriazoles
undergo competing cheletropic extrusion to furnish ketimines.
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