Basic Phosphine Ligands

By: William Sommer, ChemFiles 2007, 7.10, 3.

The use of phosphines in catalysis has been extensive for the past 50 years. Utilizing electron-rich and sterically demanding phosphines, several research groups explored their efficiency and versatility in a variety of cross-coupling reactions.1 The candidate of choice for these reactions has been P(t-Bu)3, which showed its versatility by catalyzing demanding cross-coupling such as the Heck, Negishi, Suzuki and Sonogashira reactions.2 Of particular interest, the Stille coupling reaction has been challenging especially with unactivated aryl halides. The use of P(t-Bu)3 with Pd2dba3 extended the scope of the Stille coupling with the synthesis of biaryls bearing electron-withdrawing groups (Scheme 1). Using 6 mol% of ligand and 1.5 mol% of Pd2(dba)3, the reaction produced the desired biaryls with good to excellent yields (Table 1). It is important to note that even electron donating substituents on the aryl bromide group gave excellent yields.

Stille coupling

Scheme 1

Table 1

Building on their work with bulky trialkylphosphines, Fu and coworkers explored the Hiyama transformation using one of their most versatile ligands, P(t-Bu)2Me.3 The Hiyama coupling reaction is of importance due to the use of organosilicon as reagents. Organosilicon compounds offer the advantage of being air stable and non-toxic. Furthermore, the Hiyama coupling is one of the rare reactions to couple sp2–sp3 carbons. The ligand chosen for the reaction has showed outstanding results in a variety of cross-coupling transformations. Utilizing P(t-Bu)2Me and PdBr2 a variety of alkyl bromides were coupled with arylsilicon derivatives (Scheme 2), the reaction yielded the desired coupling products with good to excellent yields (Table 2).

Hiyama coupling

Scheme 2

Table 2

Since the late 1990s several research groups have shown the versatility and efficiency of trialkyl phosphine ligands for a variety of palladium-catalyzed transformations.4 Expanding the portfolio of coupling reactions that triaryl phosphines undergo, Fu and coworkers developed a new method for the Suzuki cross-coupling of nitrogen heterocycles.5 Using as little as 1 mol% of palladium and 2.4 mol% of PCy3 (Scheme 3), the transformation yielded a variety of biaryls in good to excellent yields (Table 3). The versatility of these ligands was demonstrated with the coupling of a variety of pyridines and pentadienes.

Suzuki cross-coupling

Scheme 3

Table 3

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  1. (a) Netherton, M. R. et al. J. Am. Chem. Soc. 2001, 123, 10099. (b) Kirchhoff, J. H. et al. Angew. Chem. Int. Ed. 2002, 41, 1945.
  2. Menzel, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 3718.
  3. Lee, J.-Y.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616.
  4. Rouhi, A. M., Chem. Eng. News 2004, 82, 49.
  5. Kudo, N. et al. Angew. Chem. Int. Ed. 2006, 45, 1282.

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