Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Pd-catalyzed Suzuki–Miyaura reactions of aryl halides using bulky biarylmonophosphine ligands


The following protocol describes the application of a highly active Pd-based catalyst system in the Suzuki–Miyaura cross-coupling reaction of arylboronic acids with aryl chlorides to provide biaryl compounds. The general procedure includes a detailed description of an appropriate reaction setup, two methods for assaying the crude reaction mixture (GC and TLC) and a procedure for the isolation, purification and characterization of the anticipated product. Reagents and catalyst precursors can be manipulated in the air; however, the cross-coupling reactions must be performed in an inert atmosphere. Two Suzuki–Miyaura reactions are included in the text as representative examples of these procedures. Although the reactions can proceed in less than 5 min, the protocols, including workup, generally take 6–30 h to be completed.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12


  1. Smith, G.B., Denzeny, G.C., Hughes, D.L., King, A.O. & Verhoeven, T.R. Mechanistic studies of the Suzuki cross-coupling reaction. J. Org. Chem. 59, 8151–8156 (1994).

    CAS  Article  Google Scholar 

  2. Jacks, T.E. et al. Development of a scalable process for CI-1034, an endothelin antagonist. Org. Proc. Res. Dev. 8, 201–212 (2004).

    CAS  Article  Google Scholar 

  3. Miller, W.D., Fray, A.H., Quatroche, J.T. & Sturgill, C.D. Supression of a palladium-mediated homocoupling in a Suzuki cross-coupling reaction. Development of an impurity control strategy supporting synthesis of LY451395. Org. Proc. Res. Dev. 11, 359–364 (2007).

    CAS  Article  Google Scholar 

  4. Ise, T. et al. Light emitting element and azole compound. European patent 1,175,128 A2 (2001).

  5. de Meijere A., Diederich F., (eds.) Metal-Catalyzed Cross-Coupling Reactions 2nd edn. (Wiley-VCH, New York, 2004).

    Book  Google Scholar 

  6. Bellina, F., Carpita, A. & Rossi, R. Palladium catalysts for the Suzuki cross-coupling reaction: an overview of recent advances. Synthesis 2419–2440 (2004).

  7. Littke, A.F & Fu, G. Palladium-catalyzed coupling reactions of aryl chlorides. Angew. Chem. Int. Ed. Engl. 41, 4176–4211 (2002).

    CAS  Article  Google Scholar 

  8. Old, D.W., Wolfe, J.P. & Buchwald, S.L. A highly active catalyst for palladium-catalyzed cross-coupling reactions: room-temperature Suzuki couplings and amination of unactivated aryl chlorides. J. Am. Chem. Soc. 120, 9722–9723 (1998).

    CAS  Article  Google Scholar 

  9. Walker, S.D., Barder, T.E., Martinelli, J.R. & Buchwald, S.L. A rationally designed universal catalyst for Suzuki–Miyaura coupling processes. Angew. Chem. Int. Ed. Engl. 43, 1871–1876 (2004).

    CAS  Article  Google Scholar 

  10. Barder, T.E., Walker, S.D., Martinelli, J.R. & Buchwald, S.L. Catalysts for Suzuki–Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 127, 4685–4696 (2005).

    CAS  Article  Google Scholar 

  11. Billingsley, K.L., Anderson, K.W. & Buchwald, S.L. A highly active catalyst for Suzuki-Miyaura cross-coupling reactions of heteroaryl compounds. Angew. Chem. Int. Ed. Engl. 45, 3484–3488 (2006).

    CAS  Article  Google Scholar 

  12. Billingsley, K.L. & Buchwald, S.L. Highly efficient monophosphine-based catalyst for the palladium-catalyzed Suzuki–Miyaura reaction of heteroaryl halides and heteroaryl boronic acids and esters. J. Am. Chem. Soc. 129, 3358–3366 (2007).

    CAS  Article  Google Scholar 

  13. Nguyen, H.N., Huang, X. & Buchwald, S.L. The first general palladium catalyst for the Suzuki–Miyaura and carbonyl enolate coupling of aryl arenesulfonates. J. Am. Chem. Soc. 125, 11818–11819 (2003).

    CAS  Article  Google Scholar 

  14. Milne, J.E. & Buchwald, S.L. An extremely active catalyst for the Negishi cross-coupling reaction. J. Am. Chem. Soc. 126, 13028–13032 (2004).

    CAS  Article  Google Scholar 

  15. Martin, R. & Buchwald, S.L. Pd-catalyzed Kumada–Corriu cross-coupling reactions at low temperatures allow the use of Knochel-type Grignard reagents. J. Am. Chem. Soc. 129, 3844–3845 (2007).

    CAS  Article  Google Scholar 

  16. Anderson, K.W. & Buchwald, S.L. General catalysts for the Suzuki–Miyaura and Sonogashira coupling reactions of aryl chlorides and for the coupling of challenging substrate combinations in water. Angew. Chem. Int. Ed. Engl. 44, 6173–6177 (2005).

    CAS  Article  Google Scholar 

  17. Huang, X., Anderson, K.W., Zim, D., Jiang, L., Klapers, A. & Buchwald, S.L. 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, 6653–6655 (2003).

    CAS  Article  Google Scholar 

  18. Still, W.C., Kahn, M. & Mitra, A. Rapid chromatographic technique for preparative separations with moderate resolution. J. Org. Chem. 43, 2923–2925 (1978).

    CAS  Article  Google Scholar 

Download references


Funds for this work were provided by the National Institutes of Health (GM 46059). We also acknowledge Merck, Amgen and Boehringer Ingelheim for additional unrestricted fiscal support. We thank BASF for a gift of Pd(OAc)2. R.A.A. thanks Pfizer for a graduate fellowship.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Stephen L Buchwald.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Altman, R., Buchwald, S. Pd-catalyzed Suzuki–Miyaura reactions of aryl halides using bulky biarylmonophosphine ligands. Nat Protoc 2, 3115–3121 (2007).

Download citation

  • Published:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing