Amide-Enabled Distal and Multiple Dehydrogenative C-H Alkynylation with Tuning Site Selectivity
Bifu Liu1, Qiaoya Zhang2, Aidong Huang2
1School of Chemistry and Material Engineering, Huizhou University, Huizhou 516007, China.
Organic Letters
|July 25, 2025
Summary
We developed a new method for site-selective C-H alkynylation using amide facilitation and iridium catalysis. This approach enables precise modification of complex molecules, including pharmaceuticals like celecoxib.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Chemistry
Background:
- Site-selective modification of complex molecules presents significant synthetic challenges.
- Developing versatile methods for late-stage functionalization is crucial in drug discovery and development.
Purpose of the Study:
- To develop a novel amide-facilitated C-H alkynylation strategy.
- To achieve switchable, site-selective remote and dehydrogenative C-H alkynylation.
- To enable late-stage modification of complex drug molecules.
Main Methods:
- Utilized iridium(III) catalysis with silver(I) or copper(II) oxidants.
- Employed amide directing groups to control regioselectivity.
- Investigated directing group priority for tunable site selectivity.
Main Results:
- Successfully achieved amide-facilitated distal C-H alkynylation and dehydrogenation.
- Demonstrated switchable remote and dehydrogenative C-H alkynylation of drug molecules.
- Realized late-stage modification of celecoxib with tunable site selectivity.
Conclusions:
- The developed method offers a powerful tool for site-selective C-H functionalization.
- This strategy facilitates the modification of complex molecules, including those with challenging heterocyclic moieties.
- The approach holds promise for drug discovery and the synthesis of novel chemical entities.
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