Non-Proprietary Catalysts for Cross-Coupling

By: Josephine Nakhla, Chemfiles Volume 10 Article 3

The cross-coupling reaction of heteroaryl halides is of particular interest to the pharmaceutical industry since many biologically active compounds are accessed through use of the Suzuki-Miyaura reaction. However, the efficient coupling of five-membered heteroaryl halides or six-membered heteroaryl chlorides bearing heteroatom substituents with boronic acids has not been welldeveloped. Catalysts are thought to form inactive complexes with many of these types of substrates, and thus, they typically require high catalyst loadings in order to achieve good yields. The Guram group at Amgen has recently communicated the development of an air-stable palladium complex, (AtaPhos)2PdCl2, for Suzuki-Miyaura cross-coupling reactions. The catalyst was very effective at coupling a wide range of substrates with arylboronic acids, including aminosubstituted 2-chloropyridines and five-membered heteroaryl halides. The products are observed in excellent yields and high turnover numbers (up to 10,000 TON) are typically achieved. A series of new PdCl2{PR2(Ph-R’)}2 catalysts were developed with various reactivities.


Scheme 6. Air-stable palladium complex, (AtaPhos)2PdCl2, for Suzuki-Miyaura cross-coupling

Scheme 6. Air-stable palladium complex, (AtaPhos)2PdCl2, for Suzuki-Miyaura cross-coupling

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Materials

     

References

  1. Singer, R. A. et al. Tetrahedron Lett. 2006, 47, 3727.
  2. Singer, R. A. et al. Synthesis 2003, 1727.
  3. Guram, A. S. et al. Org. Lett. 2006, 8, 1787.

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