We are pleased to offer an array of phosphines for C-C, C-N, and C-O bond formation.

The impact of cross-coupling methodologies to form C-C bonds is paramount in organic synthesis.1 Of these, Suzuki-Miyaura coupling is among the most powerful transformations available as it enjoys broad scope and wide functional group tolerance.2 To this end, notable advances have been made in the laboratories of Prof. Stephen Buchwald at MIT. Sigma-Aldrich is proud to offer a series of Buchwald Ligands successfully utilized in processes including Suzuki-Miyaura coupling, amination, amidation, enolate arylation, Sonogashira coupling and C-O bond formation (Table 1) While each ligand has documented utility, recent work has shown that application of dimethoxy-substituted ligand 1, S-Phos, leads to a Pd-catalyst system with unprecedented scope, reactivity, and stability for Suzuki-Miyaura coupling processes.3 Selected examples (Table 2) illustrate the success of this system with respect to aryl chloride substrates, the generation of truly hindered biaryls, and heteroaryl cross-couplings.

Buchwald Phosphine Ligands

Buchwald Phosphine Ligands (Table 1)

References: 1, 4-12
Products: 638072, 638099, 638064, 638439, 638080, 638021

Aryl chloride substrates

Table 2.

Recently, triisopropyl-substituted ligand 2, X-Phos, has emerged with key applications to Pd-catalyzed C-N bond formation.4 Table 3 gives examples which typify the expanded scope of this process utilizing X-Phos. X-Phos has also been successfully applied to Suzuki-Miyaura couplings with arene and vinyl sulfonates5 (Table 2), as well as Sonogashira coupling of alkynes6 (Table 4). 2-Di-t-butylphoshino-2’,4’,6’- triisopropyl ligand has been found to be a superior ligand for Pd-catalyzed coupling of phenols with aryl bromides and chlorides.7

X-Phos

Table 3.

Sonogashira coupling of alkynes

Table 4.

Materials
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References

1.
Diedrich, F., Stang, , P. J. E, Weinhem, W. 1998. Metal-Catalyzed Cross-Coupling Reactions.
2.
Miyaura N. 2002. Organoboron Compounds.11-59. http://dx.doi.org/10.1007/3-540-45313-x_2
3.
Hassan J, Sévignon M, Gozzi C, Schulz E, Lemaire M. 2002. Aryl?Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction. Chem. Rev.. 102(5):1359-1470. http://dx.doi.org/10.1021/cr000664r
4.
Kotha S, Lahiri K, Kashinath D. 2002. Recent applications of the Suzuki?Miyaura cross-coupling reaction in organic synthesis. Tetrahedron. 58(48):9633-9695. http://dx.doi.org/10.1016/s0040-4020(02)01188-2
5.
Walker, S. R.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. . 2004. Chem. Intl. Ed., in press.  .
6.
Huang X, Anderson KW, Zim D, Jiang L, Klapars A, Buchwald SL. 2003. Expanding Pd-Catalyzed C?N Bond-Forming Processes:  The First Amidation of Aryl Sulfonates, Aqueous Amination, and Complementarity with Cu-Catalyzed Reactions. J. Am. Chem. Soc.. 125(22):6653-6655. http://dx.doi.org/10.1021/ja035483w
7.
Muci AR, Buchwald SL. 2002. Practical Palladium Catalysts for C-N and C-O Bond Formation.131-209. http://dx.doi.org/10.1007/3-540-45313-x_5
8.
Nguyen HN, Huang X, Buchwald SL. 2003. The First General Palladium Catalyst for the Suzuki?Miyaura and Carbonyl Enolate Coupling of Aryl Arenesulfonates. J. Am. Chem. Soc.. 125(39):11818-11819. http://dx.doi.org/10.1021/ja036947t
9.
Gelman D, Buchwald SL. 2003. Efficient Palladium-Catalyzed Coupling of Aryl Chlorides and Tosylates with Terminal Alkynes: Use of a Copper Cocatalyst Inhibits the Reaction. Angew. Chem. Int. Ed.. 42(48):5993-5996. http://dx.doi.org/10.1002/anie.200353015
10.
Burgos C, Buchwald SL. manuscript in preparation. .
11.
Harris MC, Huang X, Buchwald SL. 2002. Improved Functional Group Compatibility in the Palladium-Catalyzed Synthesis of Aryl Amines. Org. Lett.. 4(17):2885-2888. http://dx.doi.org/10.1021/ol0262688
12.
Wolfe JP, Tomori H, Sadighi JP, Yin J, Buchwald SL. 2000. Simple, Efficient Catalyst System for the Palladium-Catalyzed Amination of Aryl Chlorides, Bromides, and Triflates. J. Org. Chem.. 65(4):1158-1174. http://dx.doi.org/10.1021/jo991699y