Interrupted C(sp2) Ritter Reaction Enabled by a Stable Nitrilium Surrogate.
- 1School of Chemistry, University of Bristol, Cantock's Close, Bristol, AvonBS8 1TS, U.K.
Abstract
The Ritter reaction is a classic named-reaction for amide synthesis that converts alkenes or tertiary alcohols into N-alkyl amides via carbocation and nitrilium intermediates under strongly acidic conditions. Despite nearly eight decades of development, the synthetic scope remains limited by the inability to control the reactivity of the nitrilium-ion and avoid its rapid hydrolysis to amides. Here, we report a strategy to overcome this long-standing limitation by stabilizing the nitrilium intermediate as an imidoyl fluoride. β-Fluorovinyl iodonium salts, readily prepared from alkynes, undergo a stereoselective C(sp2) Ritter reaction with nitriles in the presence of silver fluoride. Mechanistic studies revealed the nitrilium surrogate to be sufficiently persistent that it could be exploited synthetically by trapping by oxygen-, sulfur-, nitrogen-, and carbon-centered nucleophiles to provide fluorovinyl enamides, imides, imidates, amidines, tetrazoles, enamines, and imines. This work establishes a rare C(sp2) Ritter reaction and demonstrates that nitrilium-ion reactivity can be controlled and diverted from hydrolysis toward productive intermolecular bond-forming processes, opening a new direction for Ritter chemistry.
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BibTeX
@article{chaturvedi2026interrupted,
title = {{Interrupted C(sp2) Ritter Reaction Enabled by a Stable Nitrilium Surrogate.}},
author = {Atul K Chaturvedi and Andrew J D Lacey and Alexi T Sedikides and Alastair J J Lennox},
journal = {Journal of the American Chemical Society},
year = {2026},
month = oct,
doi = {10.1021/jacs.6c17360},
url = {https://europepmc.org/article/MED/42912311},
note = {CC BY},
}
RIS
TY - JOUR
TI - Interrupted C(sp2) Ritter Reaction Enabled by a Stable Nitrilium Surrogate.
AU - Atul K Chaturvedi
AU - Andrew J D Lacey
AU - Alexi T Sedikides
AU - Alastair J J Lennox
PY - 2026
DA - 2026/10/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c17360
UR - https://europepmc.org/article/MED/42912311
AB - The Ritter reaction is a classic named-reaction for amide synthesis that converts alkenes or tertiary alcohols into N-alkyl amides via carbocation and nitrilium intermediates under strongly acidic conditions. Despite nearly eight decades of development, the synthetic scope remains limited by the inability to control the reactivity of the nitrilium-ion and avoid its rapid hydrolysis to amides. Here, we report a strategy to overcome this long-standing limitation by stabilizing the nitrilium intermediate as an imidoyl fluoride. β-Fluorovinyl iodonium salts, readily prepared from alkynes, undergo a stereoselective C(sp2) Ritter reaction with nitriles in the presence of silver fluoride. Mechanistic studies revealed the nitrilium surrogate to be sufficiently persistent that it could be exploited synthetically by trapping by oxygen-, sulfur-, nitrogen-, and carbon-centered nucleophiles to provide fluorovinyl enamides, imides, imidates, amidines, tetrazoles, enamines, and imines. This work establishes a rare C(sp2) Ritter reaction and demonstrates that nitrilium-ion reactivity can be controlled and diverted from hydrolysis toward productive intermolecular bond-forming processes, opening a new direction for Ritter chemistry.
SN - 0002-7863
SN - 1520-5126
ER -