Chemical Synthesis

BRIDP from Takasago



Introduction

Cross-couplings have been an essential reaction class for the past 20 years. They are used for the synthesis of a plethora of products ranging from drug molecules to polymers. Since the first report of cross-coupling catalysis by Tsuji and Trost, an exponential number of catalytic systems have been published in the ensuing years. The typical catalyst for cross-coupling reactions involves a palladium complex with a phosphine-based ligand. Among the most utilized cross-coupling reactions stand Tsuji-Trost, Suzuki-Miyaura, Negishi, Stille, and Heck-Mizoroki couplings involving the reaction of an aryl halide with an alkene or arene. The other important cross-coupling reaction is the Buchwald-Hartwig amination involving an amine and an aryl halide. This last reaction is of particular interest to the pharmaceutical industry since many biologically active compounds are accessed through this methodology. Researchers at Takasago developed new phosphine-based ligands for this reaction with successful results for the cross-coupling of a wide array of amines and aryl halides.

Advantages

  • Efficient ligands
  • Atom-economical
  • Low catalyst loading
  • Access to biaryls substituted with nitrogen

Representative Applications

Amination of Aryl Halides 

Suzuki et al. developed a new ligand for the effective amination of a variety of aryl halides.1 To develop this new ligand, the research team looked at several factors influencing the catalytic activity. Among these factors, the electron density and the steric hindrance were of utmost importance. The new ligand consists of two phenyl groups connected to a dicyclohexylphoshinylpropylidene. Aromatic amination using this ligand proved to be very effective with aryl bromides and secondary amines.



Following the results reported in 2007, using a vinyl-based phosphine ligand, Suzuki et al. reported an improved version of this ligand for the amination of a variety of aryl chlorides with primary and secondary amines.2 The new ligand has a methylcyclopropane moiety binding two phenyls to di-(tert-butyl)phosphine. This improved ligand showed improved activity with loading as low as 0.2 mol% for the amination of aryl bromides. A variety of tertiary amines were synthesized with good yields. It is important to note that electron-deficient substituents and steric hindrance on the amine or aryl halide had little influence on the yield of the reaction. 

 

X Product Yield %
Br   97
Cl   80
Cl   98
Br   91
Cl   95
Cl   94
Cl   82

References

  1. Suzuki, K. et al. Adv. Synth. Catal. 2007, 349, 2089.
  2. Suzuki, K. et al. Adv. Synth. Catal. 2008, 350, 652.


Prod. No. Product Name Structure Add to Cart

 693383

 cBRIDP

 

 

 702943

 Cy-vBRIDP

 

 

 

 702951

 Cy-cBRIDP