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Chemical Science
6
7
A. Chartoire, M. Lesieur, A. M. Z. Slawin, S. P. Nolan and C. S.
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R. B. Bedford, C. S. J. Cazin, S. J. Coles, T. Gelbrich, P. N. Horton,
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999.
expedient determination of optimal conditions for a palladiumꢀ
catalyzed reaction. To evaluate this process, the SuzukiꢀMiyaura
coupling
of
4ꢀchloroꢀ3ꢀmethylanisole
and
2,
6ꢀ
difluorophenylboronic acid was chosen as a model reaction. As
depicted in Table 5, the coupling was examined with SPhos,
RuPhos, XPhos and triphenylphosphine as supporting ligands and
with the ꢁꢀCl, ꢁꢀOMs, ꢁꢀOAc dimers, as well as Pd(OAc)2 and
Pd2(dba)3 as palladium sources. Vials of palladium source and
ligand were aged for ten minutes in 1 mL of THF and directly
10 added to a reaction tube containing the aryl halide and boronic
acid, followed by the addition of base. The results of this study
clearly indicate that XPhos is the optimal ligand for this
transformation, with the catalyst based on RuPhos also showing
moderate activity. The ꢁꢀOMs dimer is optimal as the palladium
15 source, with the chloride and acetate dimers showing some
activity. The use of Pd(OAc)2 and Pd2(dba)3 under these
conditions provided little product.
65
5
8
9
M. R. Biscoe, B. P. Fors and S. L. Buchwald, J. Am. Chem. Soc.
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70 10 J. Vicente, I. SauraꢀLlamas, M. OliviaꢀMadrid and J. GarciaꢀLopez,
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– 72.
12 J. Vicente, I. SauraꢀLlamas, J. Cuadrado, and M. Ramírez de
75
Arellano, Organometallics 2003, 22, 5513 – 5517.
13 J. Albert, L. D’Andrea, J. Granell, J. Zafrilla, M. FontꢀBardia, and X.
Solans, J. Organomet. Chem. 2005, 690, 422 – 429.
14 J. Albert, L. D’Andrea, J. Granell, J. Zafrilla, M. FontꢀBardia, and X.
Solans, J. Organomet. Chem. 2007, 692, 4895 – 4902.
80 15 T. J. Maimone, P. J. Milner, T. Kinzel, Y. Zhang, M. K. Takase and
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16 Preliminary DFT calculations show 6a to be 0.05 charge units more
electropositive than 2•L1. See supporting information
Conclusions
In conclusion we have developed a new series of palladium
20 precatalysts based on the 2ꢀaminobiphenyl mesylate palladacycle
5. These precatalysts can be prepared with a broad range of
phosphine ligands in a facile and straightforward way and can be
activated under mild conditions to generate the desired LPd(0)
species. These precatalysts are all obtained in high yields from
25 common intermediate 5, which can be synthesized from readily
available starting materials in a threeꢀstep process, which avoids
rigorous Schlenk techniques. We anticipate that these precatalysts
will considerably improve the scope of palladiumꢀcatalyzed
crossꢀcoupling reactions.
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18 H. N. Nguyen, X. Huang and S. L. Buchwald, J. Am. Chem. Soc.
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2011, 13, 2564 – 2567.
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30 Acknowledgements
This activity was supported, in part, by an educational donation
provided by Amgen for which we are grateful. We thank the
National Institutes of Health for financial support (GM46059 and
GM58160). We thank SigmaꢀAldrich for a gift of BrettPhos and
35 Johnson Matthey for a gift of Pd2(dba)3. We thank Dr. Peter
Müller for Xꢀray structural analysis. We also thank Dr. Meredith
McGowan for assistance with the preparation of the manuscript
and Dr. Alex Spokoyny for helpful discussions. The Varian 300
MHz NMR instrument used for portions of this work was
40 supported by the National Science Foundation (Grants CHE
9808061 and DBI 9729592).
26 J. Hartwig, Acc. Chem. Res. 2008, 41, 1534 – 1544.
Notes and references
a Massachusetts Institute of Technology, Department of Chemistry,
Cambridge, MA 02139, USA. sbuchwal@mit.edu
45 b Merck & Co., Inc., Global Chemistry, PO Box 2000, 126 E Lincoln
Avenue, Rahway, NJ. 07065, USA. matthew_tudge@merck.com
† Electronic Supplementary Information (ESI) available: Procedural,
spectral and Xꢀray crystallographic (CIF) data. See
DOI: 10.1039/b000000x/
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