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Selective O-Cyclization of N-Methoxy Aryl Amides with CH
Wei-Hao Rao1,2, Li-Li Jiang1, Jin-Xiao Zhao1
1College of Chemistry and Chemical Engineering , Xinyang Normal University , Xinyang 464000 , China.
Organic Letters
|September 19, 2018
Summary
This study introduces a palladium-catalyzed reaction for selective O-cyclization of N-methoxy aryl amides. The method efficiently forms new carbon-oxygen and carbon-carbon bonds simultaneously, demonstrating broad functional group tolerance.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Palladium-catalyzed C-H activation is a powerful tool for C-C and C-heteroatom bond formation.
- N-methoxy amides offer unique reactivity profiles for directing group-assisted transformations.
Purpose of the Study:
- To develop a novel palladium-catalyzed O-cyclization of N-methoxy aryl amides.
- To achieve simultaneous formation of C(sp3)-O and C(sp2)-C(sp3) bonds.
- To explore the scope and limitations of this new synthetic strategy.
Main Methods:
- Utilizing palladium catalysts for C-H activation.
- Employing dichloromethane (CH2Br2) or 1,2-dichloroethane (1,2-DCE) as alkylating agents.
- Investigating the reaction mechanism through preliminary studies.
Main Results:
- Achieved selective O-cyclization of N-methoxy aryl amides.
- Successfully forged new C(sp3)-O and C(sp2)-C(sp3) bonds in a single step.
- Demonstrated good functional group tolerance with various substrates.
Conclusions:
- The developed palladium-catalyzed C-H activation offers an efficient route for simultaneous C-O and C-C bond formation.
- The N-methoxy amide group plays a crucial role in directing the cyclization.
- The reaction proceeds possibly through a five-membered palladacycle intermediate.
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