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Amide α-C-H oxidative coupling reactions enabled by base-promoted halogen transfer
Faith E Kidd1, Cristian Vásquez Tapia Vera1, Jeffrey S Bandar1
1Department of Chemistry Colorado State University Fort Collins Colorado 80523 USA jeff.bandar@colostate.edu.
Chemical Science
|July 11, 2026
Summary
This study introduces a new method for directly coupling amide α-C-H bonds with various nucleophiles. This efficient oxidative coupling simplifies the synthesis of α-substituted amides.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Traditional synthesis of α-substituted amides often involves multi-step processes.
- Existing methods for direct functionalization of amide α-C-H bonds are challenging.
Purpose of the Study:
- To develop a novel, direct, base-promoted protocol for the oxidative coupling of amide α-C-H bonds.
- To provide a streamlined and modular alternative to conventional amide synthesis.
Main Methods:
- Utilized mild bases and inexpensive 2-bromothiophenes as halogen oxidants.
- Employed a synergistic deprotonation, halogenation, and substitution sequence.
- Achieved direct oxidative coupling of amide α-C-H bonds with O-, S-, and N-pronucleophiles.
Main Results:
- Successfully demonstrated a one-step protocol for α-functionalization of amides.
- Overcame limitations of traditional two-step enolate formation/halogenation methods.
- Enabled efficient synthesis of α-substituted amides from readily available starting materials.
Conclusions:
- The described protocol offers a significant advancement in amide synthesis.
- This method provides a versatile and efficient route to α-substituted amides.
- The approach simplifies synthetic strategies, reducing step count and improving modularity.
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