Complex Fragment Coupling via O-Mesyl Hydroxylamines: Direct Conversion of Primary Amines to Electrophilic Aminating Agents.
- 1Department of Chemistry, BioScience Research Collaborative, Rice University, 6500 Main Street, Rm 380, Houston, Texas77030, United States.
- 2Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah84602, United States.
Abstract
Nitrogen-containing molecules are ubiquitous in pharmaceuticals, natural products, ligands, and functional materials, sustaining continued interest in efficient C-N bond-forming strategies. Although electrophilic amination has emerged as a powerful complement to classical nucleophilic substitution and cross-coupling methods, the transfer of structurally complex NH-alkyl groups remains limited by the lack of general access to suitably reactive electrophilic aminating reagents. Herein, we report the direct single-step oxidation of primary amines to N-alkyl-O-mesyl hydroxylamines using dimesyl peroxide (MPO). This transformation achieves an umpolung of otherwise nucleophilic amines and provides rapid access to synthetically versatile electrophilic nitrogen building blocks under mild conditions. A broad substrate scope enables the preparation of structurally complex and chiral N-alkyl-O-mesyl hydroxylamines, including derivatives of amino acids, natural products, and pharmaceuticals. These reagents were directly deployed in established electrophilic amination manifolds, including arene C-H amination, olefin aziridination, and aza-Rubottom oxidation, enabling the transfer of structurally complex and chiral amine fragments. Collectively, this work establishes a general strategy for converting readily available primary amines into electrophilic nitrogen fragments for efficient C-N bond formation and N-electrophilic fragment coupling.
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BibTeX
@article{georg2026complex,
title = {{Complex Fragment Coupling via O-Mesyl Hydroxylamines: Direct Conversion of Primary Amines to Electrophilic Aminating Agents.}},
author = {Mats Georg and Young-Do Kwon and Mathias Boeckle and Dongdong Yang and Daniel H Ess and László Kürti},
journal = {Journal of the American Chemical Society},
year = {2026},
month = oct,
doi = {10.1021/jacs.6c14811},
url = {https://europepmc.org/article/MED/42913601},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Complex Fragment Coupling via O-Mesyl Hydroxylamines: Direct Conversion of Primary Amines to Electrophilic Aminating Agents.
AU - Mats Georg
AU - Young-Do Kwon
AU - Mathias Boeckle
AU - Dongdong Yang
AU - Daniel H Ess
AU - László Kürti
PY - 2026
DA - 2026/10/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c14811
UR - https://europepmc.org/article/MED/42913601
AB - Nitrogen-containing molecules are ubiquitous in pharmaceuticals, natural products, ligands, and functional materials, sustaining continued interest in efficient C-N bond-forming strategies. Although electrophilic amination has emerged as a powerful complement to classical nucleophilic substitution and cross-coupling methods, the transfer of structurally complex NH-alkyl groups remains limited by the lack of general access to suitably reactive electrophilic aminating reagents. Herein, we report the direct single-step oxidation of primary amines to N-alkyl-O-mesyl hydroxylamines using dimesyl peroxide (MPO). This transformation achieves an umpolung of otherwise nucleophilic amines and provides rapid access to synthetically versatile electrophilic nitrogen building blocks under mild conditions. A broad substrate scope enables the preparation of structurally complex and chiral N-alkyl-O-mesyl hydroxylamines, including derivatives of amino acids, natural products, and pharmaceuticals. These reagents were directly deployed in established electrophilic amination manifolds, including arene C-H amination, olefin aziridination, and aza-Rubottom oxidation, enabling the transfer of structurally complex and chiral amine fragments. Collectively, this work establishes a general strategy for converting readily available primary amines into electrophilic nitrogen fragments for efficient C-N bond formation and N-electrophilic fragment coupling.
SN - 0002-7863
SN - 1520-5126
ER -