Copper-catalysed site-selective arylation of pyrazoles
4 affiliations
- 1Department of Chemistry, University of California, Irvine, Irvine, CA, USA
- 2Department of Chemistry, Binghamton University, Binghamton, NY, USA
- 3Department of Chemistry, Binghamton University, Binghamton, NY, USA. [email protected]
- 4Department of Chemistry, University of California, Irvine, Irvine, CA, USA. [email protected]
Abstract
A major challenge in late-stage functionalization is the selective N-arylation of unsymmetric pyrazoles, five-membered heterocycles with two adjacent nitrogen atoms, which are prevalent in blockbuster medicines and bioactive molecules. Traditional cross-coupling methods usually favour one type of regioisomer, limiting access to complementary structures that could accelerate drug discovery and streamline structure-activity relationship studies. Here we show that copper catalysis harnesses arynes to achieve switchable arylation of pyrazoles under mild conditions. By tuning Cu-pyrazole coordination, we direct arylation to either nitrogen atom, unlocking selectivity between two similar sites. Mechanistic studies reveal how steric and electronic effects govern regioselectivity, transforming an inherently unpredictable process into a blueprint for selective recognition of N-N linkages. This approach establishes a general strategy for controlling site selectivity in nitrogen-rich heterocycles and highlights the use of strained intermediates in late-stage diversification.
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BibTeX
@article{wang2026coppercatalysed,
title = {{Copper-catalysed site-selective arylation of pyrazoles}},
author = {Minghao Wang and Xintong Hou and Stephanie A. Corio and Lori Digal and Jennifer S. Hirschi and Vy M. Dong},
journal = {Nature Chemistry},
year = {2026},
month = jun,
doi = {10.1038/s41557-026-02148-z},
url = {https://doi.org/10.1038/s41557-026-02148-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Copper-catalysed site-selective arylation of pyrazoles
AU - Minghao Wang
AU - Xintong Hou
AU - Stephanie A. Corio
AU - Lori Digal
AU - Jennifer S. Hirschi
AU - Vy M. Dong
PY - 2026
DA - 2026/06/12
JO - Nature Chemistry
DO - 10.1038/s41557-026-02148-z
UR - https://doi.org/10.1038/s41557-026-02148-z
AB - A major challenge in late-stage functionalization is the selective N-arylation of unsymmetric pyrazoles, five-membered heterocycles with two adjacent nitrogen atoms, which are prevalent in blockbuster medicines and bioactive molecules. Traditional cross-coupling methods usually favour one type of regioisomer, limiting access to complementary structures that could accelerate drug discovery and streamline structure-activity relationship studies. Here we show that copper catalysis harnesses arynes to achieve switchable arylation of pyrazoles under mild conditions. By tuning Cu-pyrazole coordination, we direct arylation to either nitrogen atom, unlocking selectivity between two similar sites. Mechanistic studies reveal how steric and electronic effects govern regioselectivity, transforming an inherently unpredictable process into a blueprint for selective recognition of N-N linkages. This approach establishes a general strategy for controlling site selectivity in nitrogen-rich heterocycles and highlights the use of strained intermediates in late-stage diversification.
SN - 1755-4330
SN - 1755-4349
ER -