Communication
Organic & Biomolecular Chemistry
substituted biaryls from aryl or naphthyl magnesium bromides
and aryl, naphthyl, heteroaryl halides exceedingly well and in
very high isolated yields. Finally, the high activity/productivity
of 7 is attributed to the very important bulk of the NHC ligand
in the coordination sphere of the palladium. To the best of our
knowledge, 7 is the most active palladium complex reported to
date for the synthesis of tetra-ortho-substituted biaryl com-
pounds via this cross-coupling reaction. Studies aimed at
expanding the scope of reactions possibly benefiting from
increased ligand bulk around the metal centre are on-going in
our laboratories.
The authors are grateful to the Royal Society (University
Research Fellowship to CSJC) for funding and to Umicore for
the gift of Pd salts. The authors also thank Prof. Luigi Cavallo
for fruitful discussions and access the SambVca application.
Notes and references
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Scheme 2 Scope of the reaction leading to tetra-ortho-substituted
biaryls. Reagents and conditions: Ar/HetX (0.5 mmol), Ar’MgBr
(0.55 mmol), 7, 1,4-dioxane (2.5 mL), 60 °C, 16 h. Isolated yields, average
of two reactions.
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[Pd(µ-Cl)Cl(SIPr)]2.12b This supports the theory that bulkier
ligands lead to more efficient systems for the formation of
sterically congested biaryls. The reaction conditions were opti-
mised (see ESI†). After 16 h at 60 °C in 1,4-dioxane and
0.1 mol% of 7, the desired cross-coupling compound 10a was
obtained in an excellent 91% isolated yield. A further decrease
of the catalyst loading to 0.05 mol% is possible, but the reac-
tion does not reach completion. Nevertheless, an acceptable
72% conversion to the desired product is obtained. The scope
of the reaction was next investigated (Scheme 2). The cross-
couplings of aryl or naphthyl magnesium bromides and aryl,
naphthyl or heteroaryl halides proceed in very good to excel-
lent isolated yields (73–98%, 22 examples), with no formation
of homo-coupling by-products. The catalyst performs equally
well with aryl chlorides or bromides, suggesting that the oxi-
dative addition of the aryl halide is not the rate-limiting step
in this reaction (10c, 10d, 10k and 10n). The highly challen-
ging dimethoxy derivative 1-chloro-2,6-dimethoxybenzene can
also be successfully coupled, however, a slightly higher operat-
ing temperature is necessary (10g). Finally, tetra-ortho-substi-
tuted C–C bonds involving heterocycles can also be formed
using the reported system (10r).
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In summary, a well-defined pre-catalyst [Pd(µ-Cl)Cl(IPr*)]2 7
bearing a very sterically demanding NHC ligand has been
isolated by a straightforward synthetic route. This complex
exhibits very high catalytic activity in the Grignard reagent
cross-coupling of very sterically demanding partners leading to
the formation of highly hindered C–C biaryl junctions. This
dimer performed the challenging formation of tetra-ortho-
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5588 | Org. Biomol. Chem., 2014, 12, 5586–5589
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