Synthesis of 15N-Labelled Complex Saturated N-Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap
- 1Department of Chemistry
- 2University of Chicago
Abstract
‡Process Research and Development, Merck & Co., Rahway, New Jersey 07065, United States ABSTRACT: Efficient construction of 15N-labelled 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 15Nenriched saturated heterocycles. This transformation is enabled by a methylsulfonyl-based 15N-labelled 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
@misc{zhang2026synthesis,
title = {{Synthesis of 15N-Labelled Complex Saturated N-Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap}},
author = {Zining Zhang and Seoung-Tae Kim and Jingwei Li and Guangbin Dong},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008499/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008499/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Synthesis of 15N-Labelled 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 - 2026/09/08
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008499/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008499/v1
AB - ‡Process Research and Development, Merck & Co., Rahway, New Jersey 07065, United States ABSTRACT: Efficient construction of 15N-labelled 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 15Nenriched saturated heterocycles. This transformation is enabled by a methylsulfonyl-based 15N-labelled 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.
ER -