Native Amide-Directed C(sp3)-H Alkynylation Using an Electron-Deficient Iridium Catalyst with Pyridone Ligand
Shunsuke Kimura1, Tomoaki Kobayashi1, Yuki Hirata1,2
1Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Organic Letters
|November 20, 2025
Summary
This study introduces a new method for C(sp3)-H alkynylation using amide-directing groups and an iridium catalyst. This approach streamlines the synthesis of complex molecules by functionalizing carbon-hydrogen bonds.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Chemistry
Background:
- Direct functionalization of C(sp3)-H bonds offers a streamlined route to complex molecules.
- Native carbonyl functional groups can direct C-H bond activation.
- Amide groups are common in biologically relevant molecules and synthetic intermediates.
Purpose of the Study:
- To develop a novel amide-directed C(sp3)-H alkynylation reaction.
- To utilize an electron-deficient iridium catalyst and pyridone ligand for this transformation.
- To achieve efficient alkynylation of methyl and methylene groups in cyclobutane carboxamides.
Main Methods:
- Employing an electron-deficient iridium catalyst.
- Utilizing an electron-deficient pyridone ligand.
- Optimizing reaction conditions for C(sp3)-H alkynylation of cyclobutane carboxamides.
Main Results:
- Successful C(sp3)-H alkynylation of terminal methyl groups.
- Successful C(sp3)-H alkynylation of internal methylene groups in cyclobutane carboxamides.
- Obtained desired products in moderate to good yields.
Conclusions:
- Demonstrated the efficacy of native amide-directed C(sp3)-H alkynylation.
- Established a new synthetic strategy for introducing alkyne moieties via C-H functionalization.
- Highlighted the potential of iridium catalysis in streamlining complex molecule synthesis.
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