Access to and unexplored reactivity of nickel-bound 5-membered O- and N-heterocyclic arynes via computational insight
- 1University of Minnesota, Department of Chemistry Minneapolis MN 55455 USA
- 2Oberlin College, Department of Chemistry and Biochemistry Oberlin Ohio 44074 USA
Abstract
N-Heterocyclic arynes are versatile but underutilized intermediates for rapidly functionalizing N-containing arenes. Part of the reason for the underutilization of N-heterocyclic arynes is that 5-membered N-heterocyclic arynes are inaccessible due to ring strain. In 2024, our group demonstrated that coordinating such strained intermediates to a metal center could stabilize the aryne bond via metal back-donation and thereby enable formation of otherwise inaccessible 5-membered heterocyclic arynes. Interestingly, heterocycles such as 4-azaindole and benzofuran that lacked subtle steric interactions were found to form borate complexes instead of the desired aryne during the key transmetallation step. Herein, we employ a computationally guided ligand approach to overcome this borate complex formation to generate the desired arynes. Using our computational findings, we accessed new previously inaccessible arynes: 4-azaindol-2,3-yne, pyrrolo-2,3-yne pyrazine, and the first ever proposed aryne, benzofuran-2,3-yne, all bound to Ni. Additionally, we report on a novel 5-membered aryne mode of reactivity in the form of a formal inverse-demand Diels–Alder reaction to yield a new class of underexplored heterocycles.
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BibTeX
@article{pullarat2026access,
title = {{Access to and unexplored reactivity of nickel-bound 5-membered O- and N-heterocyclic arynes via computational insight}},
author = {Sanu Siyad Pullarat and Ali A. Younis and Gabriel N. Morais and Matthew C. Fitzsimmons and Roman G. Belli and Jenna N. Humke and Shuming Chen and Courtney C. Roberts},
journal = {Chemical Science},
year = {2026},
month = sep,
doi = {10.1039/d6sc05533h},
url = {https://doi.org/10.1039/d6sc05533h},
note = {CC BY-NC 3.0},
}
RIS
TY - JOUR
TI - Access to and unexplored reactivity of nickel-bound 5-membered O- and N-heterocyclic arynes via computational insight
AU - Sanu Siyad Pullarat
AU - Ali A. Younis
AU - Gabriel N. Morais
AU - Matthew C. Fitzsimmons
AU - Roman G. Belli
AU - Jenna N. Humke
AU - Shuming Chen
AU - Courtney C. Roberts
PY - 2026
DA - 2026/09/14
JO - Chemical Science
DO - 10.1039/d6sc05533h
UR - https://doi.org/10.1039/d6sc05533h
AB - N-Heterocyclic arynes are versatile but underutilized intermediates for rapidly functionalizing N-containing arenes. Part of the reason for the underutilization of N-heterocyclic arynes is that 5-membered N-heterocyclic arynes are inaccessible due to ring strain. In 2024, our group demonstrated that coordinating such strained intermediates to a metal center could stabilize the aryne bond via metal back-donation and thereby enable formation of otherwise inaccessible 5-membered heterocyclic arynes. Interestingly, heterocycles such as 4-azaindole and benzofuran that lacked subtle steric interactions were found to form borate complexes instead of the desired aryne during the key transmetallation step. Herein, we employ a computationally guided ligand approach to overcome this borate complex formation to generate the desired arynes. Using our computational findings, we accessed new previously inaccessible arynes: 4-azaindol-2,3-yne, pyrrolo-2,3-yne pyrazine, and the first ever proposed aryne, benzofuran-2,3-yne, all bound to Ni. Additionally, we report on a novel 5-membered aryne mode of reactivity in the form of a formal inverse-demand Diels–Alder reaction to yield a new class of underexplored heterocycles.
SN - 2041-6520
SN - 2041-6539
ER -