Phosphine Ligands [Cross-coupling Reaction using Transition Metal Catalysts]

Phosphines are a three-valent phosphorus compound and act as a "soft" σ-donating ligand with an unshared electron pair. This gives solubilization and stabilization to organometallic complexes by forming complexes with various transition metal species including latter-period transition metals and others, and is also used for controlling the reactivity and selectivity of the transition metal promoted reactions.
Electron density and bulkiness of phosphine ligands are greatly related to the reactivity of their forming metal complexes. Generally, the phosphine ligands with high electron density increase the reactivity of oxidative addition from a metal center, and their bulkiness improves the reductive elimination. For example, trialkylphosphines especially tert-butyl or cyclohexyl group substituted phosphines show the highest electron density while the electron density of triarylphosphines and phosphite are sequentially decreasing. On the other hand, as an index of the bulkiness of phosphine ligands, that of monodentate phosphine ligands shows the cone angle (θ) while bidentate phosphine ligands show the bite angle (ω). As the angle of the phosphine ligands is wider, their steric effect is greater and they are regarded as more bulky phosphine ligands. A monodentate phosphine ligand of tri(o-tolyl)phosphine, and bidentate phosphine ligands of 1,1'-bis(diphenylphosphino)ferrocene and Xantphos are known as representative bulky phosphine ligands.

Electron rich and bulky trialkylphosphine ligands such as tri-tert-butylphosphine and tricyclohexylphosphine are highly effective to use for cross-coupling reactions due to their functionally promoting the process of catalytic cycles, both the oxidative addition and reductive elimination. For instance, aryl chlorides have low reactivity against the oxidative addition of transition metals so it generally doesn’t proceed. However, successful oxidative addition of them can be accomplished by the use of bulky trialkylphosphine ligands. In this way, trialkylphosphines have excellent chemical properties but they are unstable in air. So, it is required to handle them in a glove box. As an improvement of this disadvantage, the salt of phosphonium borates is used as a precursor of phosphine ligands. These can be treated in air and after neutralization the generated alkylphosphines are available in the reactions. Recently, alkyl group-substituted biarylphosphine ligands with higher activity have been developed and used in cross-coupling reactions. Also, unique phosphine ligands with high electron density but chemically stable in air named BRIDPs^® have been developed.²⁾

Generally, phosphines are widely used as a ligand for nickel or palladium catalysts in cross-coupling reactions. They are also effective ligands for rhodium, iridium and gold catalysts and used in catalytic reactions such as hydrogenation and cyclization reactions. Furthermore, a number of optically active phosphine ligands with chiral carbon centers, axial chirality, P-chiral center and so on, have been developed. These ligands are applied to catalytic asymmetric reactions such as asymmetric hydrogenations, asymmetric allylations, asymmetric conjugate additions, asymmetric cycloadditions and asymmetric cross-coupling reactions by the combination with various transition metal species.

References

• 1) J. F. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, Univ Science Books, 2009.
• 2) Reviews for alkylbiaryl phosphine ligands:
  • a) R. Martin, S. L. Buchwald, Acc. Chem. Res. 2008, 41, 1461.
  • b) D. S. Surry, S. L. Buchwald, Angew. Chem. Int. Ed. 2008, 47, 6338.
• 3) Review for BRIDPs^®:
  • K. Suzuki, Y. Hori, Y. Nakayama, T. Kobayashi, J. Synth. Org. Chem. Jpn. 2011, 69, 1231.