Synthesis of 15N-Labeled Complex Saturated N -Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap
- 1University of Chicago , , , ,
- 2Process Research and Development, Merck & Co. , , ,
Abstract
Efficient construction of 15N-labeled complex saturated N-heterocycles remains a substantial challenge. Here we report a late-stage carbonyl-to-15N skeletal modification strategy that converts complex cyclic ketones directly into 15N-enriched saturated heterocycles. This transformation is enabled by a methylsulfonyl-based 15N-labeled azonation reagent that suppresses unwanted overoxidation without compromising the desired C–C bond cleavage pathway. The reaction exhibits a broad substrate scope and tolerates a wide range of functional groups, serving as an effective tool for late-stage skeletal modifications of complex natural products and drug-like molecules. Mechanistic insights on the sequential double C–C activation events have been elucidated by preliminary computational studies.
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BibTeX
@article{zhang2026synthesis,
title = {{Synthesis of 15N-Labeled Complex Saturated N -Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap}},
author = {Zining Zhang and Seoung-Tae Kim and Jingwei Li and Guangbin Dong},
journal = {JACS Au},
year = {2026},
month = nov,
doi = {10.1021/jacsau.6c01410},
url = {https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01410/5463353/Synthesis-of-15N-Labeled-Complex-Saturated-N},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Synthesis of 15N-Labeled Complex Saturated N -Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap
AU - Zining Zhang
AU - Seoung-Tae Kim
AU - Jingwei Li
AU - Guangbin Dong
PY - 2026
DA - 2026/11/03
JO - JACS Au
DO - 10.1021/jacsau.6c01410
UR - https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01410/5463353/Synthesis-of-15N-Labeled-Complex-Saturated-N
AB - Efficient construction of 15N-labeled complex saturated N-heterocycles remains a substantial challenge. Here we report a late-stage carbonyl-to-15N skeletal modification strategy that converts complex cyclic ketones directly into 15N-enriched saturated heterocycles. This transformation is enabled by a methylsulfonyl-based 15N-labeled azonation reagent that suppresses unwanted overoxidation without compromising the desired C–C bond cleavage pathway. The reaction exhibits a broad substrate scope and tolerates a wide range of functional groups, serving as an effective tool for late-stage skeletal modifications of complex natural products and drug-like molecules. Mechanistic insights on the sequential double C–C activation events have been elucidated by preliminary computational studies.
SN - 2691-3704
ER -