Carbon-carbon bond forming reactions represent a useful class of transformations in the field of synthetic chemistry. For these reactions to proceed through a cross-coupling mechanism, a transition-metal and ligand are usually required. While these reactions were traditionally conducted with copper catalysts, 1-3 most modern approaches utilize palladium catalysis.4,5 These modern efforts would go on to receive the Nobel Prize in Chemistry in 2010.6-8
As research into these cross-coupling reactions took off, a number of pre-catalysts, catalysts and ligands were developed. Of particular note, the dialkylaryl phosphine ligands or Buchwald ligands, were extensively derivatized. Here, we would like to highlight the XPhos ligand (L). Structures of different generations of pre-catalysts using the XPhos ligand are depicted in Figure 1 and method of activation provided in Scheme 1.
Figure 1: Structures of Palladium Pre-Catalysts
Scheme 1: Activation of Buchwald XPhos Pre-Catalyst
The XPhos ligand and associated palladium catalysts have been utilized in a number of different cross-coupling reactions. Eq 1 shows a Negishi cross-coupling under mild conditions9 and eq 2 offers a flexible Suzuki-Miyaura coupling followed by hydrogenation of the resultant olefin.10 This second equation allows for the construction of pharmaceutically relevant molecules enriched in sp3 character.
Scheme 2: Cross-Coupling Reactions Utilizing Palladium XPhos Pre-Catalysts
Chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl] palladium(II) methyl-t-butylether adduct, min. 98% [XPhos Palladacycle Gen. 1] (1334385-47-5)
Generation II: 46-0281
Chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl) palladium(II), min. 98% [XPhos Palladacycle Gen. 2] (1310584-14-5)
Generation III: 46-0323
Methanesulfonato(2-di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II), min. 98% [t-BuXPhos Palladacycle Gen. 3] (1447963-75-8)
Methanesulfonato(2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)(2′-methylamino-1,1′-biphenyl-2-yl)palladium(II), min. 98% [XPhos Palladacycle Gen. 4] (1599466-81-5)
1. Ann. Chim. Paris, 1957, 2, 819.
2. J. Org. Chem.,1963, 28, 3313.
3. J. Am. Chem. Soc., 1967, 89, 3911.
4. J. Am. Chem. Soc., 1972, 94, 4374.
5. Tetrahedron Lett. , 1979, 20, 3437.
6. Angew. Chem. Int. Ed., 2012, 51, 5062.
7. Chem. Rev. 2007, 107, 133.
8. Nature, 2008, 41, 314.
9. Angew. Chem. Int. Ed., 2013, 52, 615.
10. Chem. Comm., 2018, 54, 46.
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