Copper-Mediated Nitrogen-Atom Migration into Saturated Carbocycles.
- 1Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin53706, United States.
Abstract
The conversion of carbocyclic rings into medicinally significant heterocycles represents a promising emerging strategy for molecular remodeling of pharmaceutical lead compounds. The selective activation and functionalization of C(sp3)-C(sp3) bonds, however, remains a formidable challenge for generalizing these methods to saturated rings. We report an operationally straightforward, one-step method for the formal insertion of nitrogen atoms into the skeletal cores of saturated carbocycles. This method leverages the underexplored ability of nitrogen-centered radical intermediates to trigger deconstructive β-scission events, and we have discovered a Cu(II) system that both generates nitrogen-centered radicals directly from sulfonamides and mediates the oxidative cyclization of the ring-opened organoradical intermediates. Given its broad functional group tolerance, scalability, and capacity for late-stage scaffold-hopping, this strategy establishes nitrogen-centered radical-mediated β-scission as a viable, general tool for the synthesis of nitrogen heterocycles by skeletal editing.
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BibTeX
@article{zeiler2026coppermediated,
title = {{Copper-Mediated Nitrogen-Atom Migration into Saturated Carbocycles.}},
author = {Michael J Zeiler and Matthieu F Maciejewski and Cade A MacAllister and Tehshik P Yoon},
journal = {Journal of the American Chemical Society},
year = {2026},
month = oct,
doi = {10.1021/jacs.6c15884},
url = {https://europepmc.org/article/MED/42912310},
note = {CC BY},
}
RIS
TY - JOUR
TI - Copper-Mediated Nitrogen-Atom Migration into Saturated Carbocycles.
AU - Michael J Zeiler
AU - Matthieu F Maciejewski
AU - Cade A MacAllister
AU - Tehshik P Yoon
PY - 2026
DA - 2026/10/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c15884
UR - https://europepmc.org/article/MED/42912310
AB - The conversion of carbocyclic rings into medicinally significant heterocycles represents a promising emerging strategy for molecular remodeling of pharmaceutical lead compounds. The selective activation and functionalization of C(sp3)-C(sp3) bonds, however, remains a formidable challenge for generalizing these methods to saturated rings. We report an operationally straightforward, one-step method for the formal insertion of nitrogen atoms into the skeletal cores of saturated carbocycles. This method leverages the underexplored ability of nitrogen-centered radical intermediates to trigger deconstructive β-scission events, and we have discovered a Cu(II) system that both generates nitrogen-centered radicals directly from sulfonamides and mediates the oxidative cyclization of the ring-opened organoradical intermediates. Given its broad functional group tolerance, scalability, and capacity for late-stage scaffold-hopping, this strategy establishes nitrogen-centered radical-mediated β-scission as a viable, general tool for the synthesis of nitrogen heterocycles by skeletal editing.
SN - 0002-7863
SN - 1520-5126
ER -