M. Mastalir, K. Kirchner
phenyl magnesium bromide and phenyl zinc bromide in
THF at room temperature and 60 °C, respectively, for 6 h
was investigated with a catalyst loading of 2 mol% to
identify the most efficient catalyst for these coupling
reactions (Tables 1, 2). In the case of the Negishi coupling,
LiCl was added to enhance the reactivity of the phenyl zinc
bromide following a procedure developed by Knochel and
co-workers [33]. In both type of reactions complex 4 turned
out to the best catalyst affording 96 and 94% isolated yields
of 4-methylbiphenyl (Tables 1, 2, entry 4), while the pyr-
idine-based complex 1 was the least active one (Tables 1,
procedures [34].The deuterated solvents were purchased from
˚
Aldrich and dried over 4 A molecular sieves. The complexes
were prepared according to the literature [27, 35]. All organic
substrates, organomagnesium, and organozinc reagents are
known compounds and were used as obtained from com-
1
13
1
mercial sources. Room temperature H and C{ H} NMR
spectra were recorded on Bruker AVANCE-250 and
1
13
1
AVANCE-400 spectrometers. H and C{ H} NMR spectra
were referenced internally to residual protio-solvent, and
solvent resonances, respectively, and are reported relative to
tetramethylsilane (d = 0 ppm). A Biotage Initiator Classic
system with auto sampler was used for the microwave reac-
tion. As reaction vessel screw cap vials were used. Column
chromatography was performed on silica gel 60 from Merck.
For thin layer chromatography (TLC) aluminum backed silica
gel was used.
2
, entry 1). Moreover, based on a negative mercury drop
test, we believe that the pincer complexes are the direct
catalyst of the reactions and that the reactions proceed in a
homogeneous fashion.
Accordingly, the potential of 4 as catalyst was evaluated
for the coupling of various aryl and heteroaryl halides (in-
cluding chlorides) and pseudohalides (triflates, tosylates)
with phenyl magnesium bromide and phenyl zinc bromide,
respectively. The results of the couplings catalyzed by
complex 4 are summarized in Table 3. In general, good to
excellent isolated yields were observed for most substrates
containing electron donating groups (OMe, Table 3, entries
General procedure for the Kumada–Corriu cross-
coupling
Substrate (0.1 mmol) and catalyst (2 mol%, 2 lmol) were
3
mixed in 3 cm
THF, organomagnesium reagent
(1.3 mmol) was added at room temperature. After 6 h at
3
8
–13) or electron withdrawing groups (acyl, Table 3, entry
4). Also heteroaryl halides, based on benzoxazole, thiazole,
60 °C, 1.5 cm NaCl solution (15%) was added carefully,
1
the organic layer was dried over MgSO , evaporated and
4
pyridine, and thiophene, afforded good yields (Table 3,
entries 15–24). Moreover, we tested the reactivity of non-
activated primary and secondary aliphatic triflates (Table 3,
entries 28–30). This reaction proceeds in good to moderate
isolated yields in the case of the Negishi coupling (Table 3,
entries 28 and 30). With butyl triflate under Kumada–Corriu
conditions, a lower yield was observed (Table 3, entry 29).
The lower yield may be due to elimination reactions of the
alkyl chain under basic conditions. Finally, the vinylation of
purified via silica column chromatography.
General procedure for the Negishi cross-coupling
Substrate (0.1 mmol) and catalyst (2 mol%, 2 lmol) were
mixed in 3 cm THF, organozinc reagent (1.3 mmol), and
3
LiCl (1.3 mmol) were added at room temperature. After
6 h at 60 °C, the solution was allowed to reach room
temperature. NaCl solution (15%, 1 cm ) was added
3
4
-bromotoluene and 4-tolyl-4-methylbenzenesulfonate with
vinyl magnesium bromide afforded high yields of
-methylstyrene (Table 3, entries 25 and 26).
carefully, the organic layer was dried over MgSO , evap-
4
orated and purified via silica column chromatography.
4
Acknowledgements Open access funding provided by Austrian
Science Fund (FWF). Financial support by the Austrian Science Fund
(FWF) (Project No. P28866-N34) is gratefully acknowledged.
Conclusion
Open Access This article is distributed under the terms of the
use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
In conclusion, we have developed a convenient and prac-
tical protocol for the Kumada–Corriu and Negishi cross-
coupling reaction of challenging electrophiles such as aryl,
heteroaryl, and alkyl halides and pseudohalides catalyzed
by an air-stable Ni(II) PNP pincer complex based on a tri-
azine scaffold.
References
Experimental
1
. de Meijere A, Diederich F (eds) (2004) Metal-Catalyzed Cross
coupling Reactions. Wiley-VCH, New York
All manipulations were performed under an inert atmosphere
of argon using Schlenk techniques or in a MBraun inert-gas
glovebox. The solvents were purified according to standard
2. Tamao K, Sumitani K, Kumada M (1972) J Am Chem Soc
4:4374
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1
23