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. 2008 Nov 18;41(11):1555-64.
doi: 10.1021/ar800148f.

The development of versatile methods for palladium-catalyzed coupling reactions of aryl electrophiles through the use of P(t-Bu)3 and PCy3 as ligands

Gregory C Fu  1
Affiliations

The development of versatile methods for palladium-catalyzed coupling reactions of aryl electrophiles through the use of P(t-Bu)3 and PCy3 as ligands

Gregory C Fu. Acc Chem Res. .

Abstract

Metal-catalyzed coupling reactions of aryl electrophiles with organometallics and with olefins serve as unusually effective tools for forming new carbon-carbon bonds. By 1998, researchers had developed catalysts that achieved reactions of aryl iodides, bromides, and triflates. Nevertheless, many noteworthy challenges remained; among them were couplings of aryl iodides, bromides, and triflates under mild conditions (at room temperature, for example), couplings of hindered reaction partners, and couplings of inexpensive aryl chlorides. This Account highlights some of the progress that has been made in our laboratory over the past decade, largely through the appropriate choice of ligand, in achieving these synthetic objectives. In particular, we have established that palladium in combination with a bulky trialkylphosphine accomplishes a broad spectrum of coupling processes, including Suzuki, Stille, Negishi, and Heck reactions. These methods have been applied in a wide array of settings, such as natural-product synthesis, materials science, and bioorganic chemistry.

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Figures

Figure 1
Figure 1
Metal-catalyzed cross-coupling reactions, including a generalized catalytic cycle for a palladium-catalyzed process.
Figure 2
Figure 2
Metal-catalyzed Heck reactions, including a generalized catalytic cycle for a palladium-catalyzed process.
Figure 3
Figure 3
Application of Pd/P(t-Bu)3 to a Stille cross-coupling: A diastereoselective macrocyclization en route to chloropeptin I (Snapper and Hoveyda).
Figure 4
Figure 4
Synthesis and stability of phosphonium salts.
Figure 5
Figure 5
Phosphonium salts as substitutes for phosphines.
See this image and copyright information in PMC

References

    1. For early reviews, see:Diederich F, Stang PJ, editors. Metal-Catalyzed Cross-Coupling Reactions. Wiley-VCH; New York: 1998. Tsuji J. Palladium Reagents and Catalysts, Innovations in Organic Synthesis. Wiley; New York: 1995.

    1. For more recent reviews, see:Tsuji J, editor. Topics in Organometallic Chemistry: Palladium in Organic Synthesis. Springer; New York: 2005. de Meijere A, Diederich F, editors. Metal-Catalyzed Cross-Coupling Reactions. Wiley-VCH; New York: 2004. Negishi E.-i., editor. Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley Interscience; New York: 2002. Miyaura N, editor. Cross-Coupling Reactions. A Practical Guide. Springer-Verlag; Berlin: 2002.

    1. For reviews of coupling reactions of aryl chlorides, see:Littke AF, Fu GC. Palladium-Catalyzed Coupling Reactions of Aryl Chlorides. Angew. Chem., Int. Ed. 2002;41:4176–4211.Grushin VV, Alper H. Activation of Otherwise Unreactive C-Cl Bonds. In: Murai S, editor. Activation of Unreactive Bonds and Organic Synthesis. Springer-Verlag; Berlin: 1999. pp. 193–226.

    1. During the past decade, powerful new catalysts for coupling reactions have been developed by a number of groups. Due to space limitations, it will not be possible to summarize in this Account the exciting discoveries of other laboratories. For an overview of early work, see Reference .

    1. Luo Y-R. Handbook of Bond Dissociation Energies in Organic Compounds. CRC Press; New York: 2003.

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