Umpolung Amide Synthesis with Nitrosoalkane Electrophiles: Pursuit of the Elusive N‑Acyl Nitrone for Dipolar Cycloadditions
- 1Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States
Abstract
Nitrones are reactive dipoles for cycloadditions that have been used for powerful alkene difunctionalization reactions, often stereocontrolled. Despite the wealth of knowledge generated over a half-century of study, reports of N-acyl nitrones are exceedingly rare, with limited options for their access. We report a new diverted Umpolung Amide Synthesis (UmAS) reaction that leads to N-acyl nitrones through an intermolecular carbon–nitrogen bond formation. These nitrones are rare examples of doubly acylated species (C- and N-acyl) that are expected to engage electron-rich alkenes in Type III dipolar cycloadditions. Our findings suggest, unexpectedly, that these species are more fleeting than previously reported, succumbing to a rapid N→O acyl transfer reaction that leads to stable O-acyl oximes.
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BibTeX
@article{benner2026umpolung,
title = {{Umpolung Amide Synthesis with Nitrosoalkane Electrophiles: Pursuit of the Elusive N‑Acyl Nitrone for Dipolar Cycloadditions}},
author = {Jeffrey S. Benner and Jeffrey N. Johnston},
journal = {The Journal of Organic Chemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.joc.6c01600},
url = {https://doi.org/10.1021/acs.joc.6c01600},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Umpolung Amide Synthesis with Nitrosoalkane Electrophiles: Pursuit of the Elusive N‑Acyl Nitrone for Dipolar Cycloadditions
AU - Jeffrey S. Benner
AU - Jeffrey N. Johnston
PY - 2026
DA - 2026/10/08
JO - The Journal of Organic Chemistry
DO - 10.1021/acs.joc.6c01600
UR - https://doi.org/10.1021/acs.joc.6c01600
AB - Nitrones are reactive dipoles for cycloadditions that have been used for powerful alkene difunctionalization reactions, often stereocontrolled. Despite the wealth of knowledge generated over a half-century of study, reports of N-acyl nitrones are exceedingly rare, with limited options for their access. We report a new diverted Umpolung Amide Synthesis (UmAS) reaction that leads to N-acyl nitrones through an intermolecular carbon–nitrogen bond formation. These nitrones are rare examples of doubly acylated species (C- and N-acyl) that are expected to engage electron-rich alkenes in Type III dipolar cycloadditions. Our findings suggest, unexpectedly, that these species are more fleeting than previously reported, succumbing to a rapid N→O acyl transfer reaction that leads to stable O-acyl oximes.
SN - 0022-3263
SN - 1520-6904
ER -