BRIDP Catalysts

By: Josephine Nakhla, Aldrich ChemFiles 2009, 9.2, 11.

Aldrich ChemFiles 2009, 9.2, 11.

Researchers at Takasago developed two phosphine-based ligands for the Buchwald-Hartwig amination reaction with successful results for the cross-coupling of a wide array of amines and aryl halides. These ligands exhibit several noteworthy advantages, with regard to efficiency and turnover numbers, as well as the ability to access biaryls substituted with a nitrogen atom.

The development of a new ligand for efficient amination of a variety of aryl halides focused on optimizing the sterics and electronics and ultimately resulted in the development of a phosphinebased ligand consisting of two phenyl groups connected to a dicyclohexylphoshinylpropylidene (Cy-vBRIDP (Scheme 7)). N-Arylation using Cy-vBRIDP was exceptionally effective with aryl bromides and secondary amines.1a


Scheme 7.

After the report of Cy-vBRIDP incorporating a vinyl-based phosphine ligand, Suzuki and co-workers reported another amination ligand (cBRIDP) for use with more challenging coupling partners such as the reaction of aryl chlorides with primary and secondary amines.2 The vinyl component was replaced with a methylcyclopropane moiety and the cyclohexyl groups were replaced with t-butyl functionalities (the cyclohexyl version of this was also developed, Cy-cBRIDP). Improved catalytic activity was demonstrated with cBRIDP, with loadings as low as 0.2 mol% achieved and generating a variety of tertiary amines in good-to-excellent yields. In addition, cBRIDP proved to be a highly general ligand, facilitating couplings with different electron-poor and electron-rich aryl bromides and chlorides (Table 2 and Table 3). Additionally, sterically hindered couplings were effected such as the coupling between 2,4,6-trichlorobenzene and carbazole, yielding sterically congested products in good yields (Scheme 8).1b


Table 2.


Table 3.


Scheme 8.

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Materials

     

References

  1. (a) Suzuki, K. et al. Adv. Synth. Catal. 2007, 349, 2089. (b) Suzuki, K. et al. Adv. Synth. Catal. 2008, 350, 652.
  2. Lewis, J. C. et al. J. Am. Chem. Soc. 2008, 130, 2493.

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