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"Cationic" Suzuki-Miyaura Coupling with Acutely Base-Sensitive Boronic Acids.
Liye Chen1, Daniel R Sanchez1, Bufan Zhang1
1Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Journal of the American Chemical Society
|September 2, 2017
Summary
This study introduces a novel, base-free Suzuki-Miyaura coupling (SMC) method. This advancement enables the efficient coupling of sensitive boronic acids, including challenging polyfluoroaryl compounds, under mild conditions.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Protodeboronation of boronic acids, especially polyfluoroaryl and heteroaryl types, is a common issue in Suzuki-Miyaura coupling (SMC).
- Traditional SMC requires a base, which can lead to undesired side reactions with sensitive substrates.
- A base-free method is needed to broaden the scope of SMC for complex molecules.
Purpose of the Study:
- To develop a novel, base-free Suzuki-Miyaura coupling (SMC) method.
- To enable the coupling of sensitive boronic acids, particularly polyfluoroaryl and heteroaryl substrates.
- To investigate the mechanism of this new SMC approach.
Main Methods:
- Development of a "cationic" SMC protocol using a PAd3-Pd catalyst.
- Reaction optimization to proceed at room temperature (rt) without a base or metal mediator.
- Stoichiometric experiments to elucidate reaction intermediates.
Main Results:
- Successful base-free SMC achieved with a PAd3-Pd catalyst at room temperature.
- A wide range of sensitive boronic acids, including polyfluoroaryl and heteroaryl compounds, were coupled cleanly.
- Evidence supporting the intermediacy of organopalladium cations was obtained.
Conclusions:
- A novel, base-free cationic SMC method has been established.
- This method overcomes limitations associated with base-promoted protodeboronation.
- The findings support a cationic pathway for transmetalation in SMC, advancing mechanistic understanding.
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