Copper-catalyzed methylative difunctionalization of alkenes
Xu Bao1, Takayuki Yokoe1, Tu M Ha1
1Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH5304, Lausanne, CH-1015, Switzerland.
Nature Communications
|September 15, 2018
Summary
Copper-catalyzed reactions enable methylative difunctionalization of alkenes, a previously unexplored area. This study introduces novel methods for synthesizing important heterocycles and generating quaternary carbon centers using readily available methyl sources.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Trifluoromethylative and hydrofunctionalization of alkenes are established synthetic methods.
- Methylative difunctionalization of olefins remains an underexplored research area, limiting synthetic strategies.
Purpose of the Study:
- To develop novel copper-catalyzed methylative difunctionalization and hydrofunctionalization of unactivated alkenes.
- To establish efficient synthetic routes for constructing complex heterocycles with quaternary carbon centers.
Main Methods:
- Copper-catalyzed alkoxy methylation and azido methylation of alkenes using peroxide-based methyl sources (dicumyl peroxide and di-tert-butyl peroxide).
- Application of developed methods to functionalized alkenes with tethered nucleophiles for intramolecular cyclization reactions.
Main Results:
- Successful development of methylative cycloetherification, lactonization, and cycloamination reactions.
- Synthesis of diverse heterocycles, including 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, γ-lactones, and pyrrolidines.
- Concurrent generation of quaternary carbon centers during heterocycle synthesis.
Conclusions:
- The developed copper-catalyzed methods provide a new avenue for methylative difunctionalization of alkenes.
- The study expands the synthetic toolbox for constructing valuable heterocyclic compounds and quaternary carbon centers.
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