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γ-Selective C(sp3)-H amination via controlled migratory hydroamination
Changseok Lee1,2, Huiyeong Seo1,2, Jinwon Jeon1,2
1Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
Nature Communications
|September 28, 2021
Summary
This study introduces a new method for remote alkene functionalization, enabling the addition of amine groups at the gamma-position of aliphatic chains through nickel-hydride-catalyzed chain walking.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Remote C(sp3)-H functionalization of alkenes is challenging, especially at the gamma-position.
- Existing methods are limited to C-H bonds near polar groups.
Purpose of the Study:
- To develop a novel method for gamma-selective C(sp3)-H amination of unactivated alkenes.
- To enable late-stage functionalization of aliphatic chains.
Main Methods:
- Nickel-hydride (NiH) catalyzed migratory formal hydroamination.
- Chelation-assisted control using directing groups (e.g., 8-aminoquinoline).
- Ligand and directing group optimization for olefin isomerization and amination selectivity.
Main Results:
- Achieved gamma-selective amination of alkenes via controlled chain walking.
- Demonstrated installation of various amine groups at the gamma-C(sp3)-H bond.
- Extended the methodology to delta-selective amination using picolinamide substrates.
- Investigated the mechanism and selectivity through experimental and computational studies.
Conclusions:
- The developed NiH-catalyzed method provides a versatile route for remote C(sp3)-H amination.
- This approach allows for late-stage synthesis of value-added gamma-aminated products.
- The methodology offers precise control over functionalization site through directed chain walking.
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