Job/Unit: O30729
/KAP1
Date: 20-08-13 11:24:07
Pages: 10
Practical Synthesis of SimplePhos Ligands
[3] L. Palais, C. Bournaud, L. Micouin, A. Alexakis, Chem. Eur.
J. 2010, 16, 2567–2573.
Experimental Section
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Synthesis 2009, 2101–2112; b) R. Millet, T. Bernardez, L. Pa-
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New Procedure for the Synthesis of SimplePhos Ligands (Exem-
plified for L4): nBuLi (14.1 mL, 22.5 mmol, 1.6 m solution in hex-
anes, 2.25 equiv.) was added to a solution of 1-bromo-3,5-dimeth-
ylbenzene (11; 3.14 mL, 4.26 g, 23.0 mmol, 2.4 equiv.) in diethyl
ether (25 mL) and stirred for 4 h at 0 °C resulting in a white suspen-
sion of aryllithium 13. In the meantime, nBuLi (8.90 mL,
14.2 mmol, 1.05 equiv.) was slowly added to a solution of amine 4
(4.62 g, 14.2 mmol, 1.05 equiv.) in THF (40 mL) at –78 °C and
stirred for 10 min, which resulted in a bright-red solution. PCl3
(1.17 mL, 1.84 g, 13.5 mmol, 1.0 equiv.) was added neat to the
amide solution at –78 °C and the solution turned yellow. After
5 min, the complete consumption of PCl3 was verified by 31P NMR
analysis (single peak at 166.5 ppm/C6D6), which indicated the com-
plete formation of dichlorophosphanamine 5. Then a solution of
aryllithium reagent 13 (described above) was added at –78 °C to
the solution of the dichlorophosphanamine 5. After immediate re-
moval of the cooling bath, warming to room temp., and stirring
for 30 min, 31P NMR analysis showed the formation of the desired
ligand L4 as a single peak (δ =43.8 ppm in C6D6). The reaction
mixture was quenched with MeOH (0.2 mL) and the solvents were
removed under reduced pressure. The residue was diluted with
CH2Cl2 (50 mL), the lithium salts removed by filtration of the sus-
pension over Celite, rinsing with additional CH2Cl2 (100 mL), and
evaporation of CH2Cl2 under reduced pressure afforded the crude
product as a yellow viscous oil. Column chromatography over tri-
ethylamine-treated silica gel (pentane/Et2O = 60:1 to 10:1; Rf =
0.74 in pentane/Et2O = 10:1), afforded L4 as a white foam (4.96 g,
8.8 mmol, 65%). The ligand can be stored over several months in
air at –40 °C without any evidence of oxidation. The triethylamine-
treated silica gel was prepared by addition of NEt3 (2.0 mL) and
pentane (100 mL) to silica gel (100 mL) and then the slurry was
filtered and dissolved in the eluent used for column chromatog-
raphy.
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1400–1402; Angew. Chem. Int. Ed. 2005, 44, 1376–1378.
For a lower yielding (63%) protocol using recrystallization
techniques for purification, see: A. Alexakis, S. Gille, F. Prian,
S. Rosset, K. Ditrich, Tetrahedron Lett. 2004, 45, 1449–1451.
Bis(3,5-dimethylphenyl)chlorophosphane, price: 500 mg, 88 j
(Sigma Aldrich, 2013).
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[14] In the preparation of the aryl-Grignard reagent, avoiding the
use of THF as solvent generally leads to lower yields of the
chlorodiarylphosphane: a) C. Whitaker, K. Kott, R. McMa-
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and NMR spectra for all com-
pounds.
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349, 1150–1158.
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[18] 4-Bromo-2,6-dimethylanisole, price: 1 g, 21 j (Sigma Aldrich,
2013).
Acknowledgments
The authors thank the Swiss National Research Foundation (grant
number 200020-126663) and COST action D40 (SER contract
number C07.0097) for financial support, as well as BASF for the
generous gift of chiral amines. The authors thank Hailing Li for
the synthesis and analytical data of ligands L29 and L30.
[19] Unpublished results.
[20] R. B. Moffett, Org. Synth. 1963, 4, 238–243.
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[23] CCDC-934087 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[1] C. Bournaud, C. Falciola, T. Lecourt, S. Rosset, A. Alexakis,
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[2] L. Palais, I. S. Mikhel, C. Bournaud, L. Micouin, C. A. Falci-
ola, M. Vuagnoux d’Augustin, S. Rosset, G. Bernardinelli, A.
Alexakis, Angew. Chem. 2007, 119, 7606–7609; Angew. Chem.
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[24] H. Li, D. Müller, L. Guénée, A. Alexakis, Org. Lett. 2012, 14,
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Received: May 17, 2013
Published Online:
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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