Structure-reactivity relationships in negishi cross-coupling reactions

Area of Science:

• Organic Chemistry
• Catalysis
• Organometallic Chemistry

Background:

• The Negishi cross-coupling reaction is a vital tool in organic synthesis for forming carbon-carbon bonds.
• Understanding the factors influencing the reactivity of substrates and reagents is crucial for optimizing catalytic processes.

Purpose of the Study:

• To investigate the relative reactivities of substituted bromobenzenes and arylzinc reagents in palladium-catalyzed Negishi cross-coupling.
• To elucidate the electronic effects of substituents on both coupling partners.

Main Methods:

• Utilized competition experiments to directly compare reaction rates.
• Employed tetrakis(triphenylphosphine)palladium(0) [Pd(PPh(3))(4)] as the catalyst in tetrahydrofuran (THF) at 25°C.
• Analyzed substituent effects using Hammett correlations.

Main Results:

• Electron-withdrawing groups on bromobenzenes accelerated the cross-coupling, with reactivity increasing from ortho to para substitution.
• Electron-withdrawing groups on arylzinc halides decreased the reaction rates.
• Hammett analysis indicated a stronger influence of substituents on bromobenzenes (ρ=+2.5) compared to arylzinc halides (ρ=-0.98).

Conclusions:

• Substituent electronic effects play a differential role in the Negishi cross-coupling mechanism, impacting bromobenzene and arylzinc halide reactivity differently.
• The findings provide valuable insights for designing and optimizing palladium-catalyzed cross-coupling reactions by controlling electronic properties of substrates.