Non-Proprietary Catalysts for Cross-Coupling

By: Josephine Nakhla, Aldrich ChemFiles 2009, 9.2, 12.

Aldrich ChemFiles 2009, 9.2, 12.

Great strides have been made in the development of catalysts for cross-coupling chemistry, particularly for Suzuki-Miyaura reactions. 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 well-developed. 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 (Table 6). The catalyst was very effective at coupling a wide variety of substrates with arylboronic acids, including amino-substituted 2-chloropyridines and fivemembered heteroaryl halides. The products are observed in excellent yields and high turnover numbers (up to 10,000 TON) are typically achieved.1

Table 6.

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  1. (a) Singer, R. A. et al. Tetrahedron Lett. 2006, 47, 3727. (b) Singer, R. A. et al. Synthesis 2003, 1727. (c) Guram, A. S. et al. Org. Lett. 2006, 8, 1787.

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