10.1002/anie.201711990
Angewandte Chemie International Edition
In addition, we sought to extend this Barbier-Negishi coupling
to 1° alkyl bromides (Scheme 2). Surprisingly, the reaction of 1-
bromopentane 11c with aryl nonaflate 10a in the presence of the
same ligand as above (L1) was inefficient, leading mainly to the
homocoupling of 10a. Fortunately, after a brief screen of other
azole-based ligands,[22] we found that less electron-rich pyrrazole-
based phosphines afforded a solution to this problem. In particular,
using L9 as the ligand allowed performing the Barbier-Negishi
coupling of 1° alkyl bromides 11a-d with nonaflate 10a in excellent
yields (Scheme 2).
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OMe
OMe
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An alternative approach consists of using first row transition-metals
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Pd2dba3 (5 mol%)
L9 (10 mol%)
( )n
Br
R
Mg, LiCl, ZnCl2,
THF, 25 °C, 24 h
12a: n = 2, 93%
12b: n = 3, 95%
12c: n = 4, 90%
ONf
10a
(1 mmol)
11a-d
(2 mmol)
N
OMe
PCy2
N
i-PrO
Oi-Pr
( )4
EtO2C
12d: 94%
L9
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Scheme 2. Barbier-Negishi coupling of 1° alkyl halides.
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In conclusion, we reported the development of the Barbier-
Negishi coupling of 2° alkyl bromides with (hetero)aryl triflates and
nonaflates under mild, non-aqueous conditions. The use of a very
bulky imidazole-based phosphine ligand allowed achieving good
yields, chemo- and site-selectivities for a broad range of substrates.
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Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
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Acknowledgments
This work was financially supported by the China Scholarship
Council (201406250018), the Swiss National Science Foundation
(200021_165987) and the University of Basel. We thank Dr. D.
Häussinger for NMR experiments, S. Mittelheisser and Dr. H. Nadig
for MS analyses, Dr. J. Rotzler, Dr. J. Schranck (Solvias AG) and
Dr. Fabrice Gallou (Novartis) for helpful discussions.
Keywords: cross-coupling · palladium · synthetic methods
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