Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8225–8228
Synthesis of diarylmethane derivatives from Pd-catalyzed
cross-coupling reactions of benzylic halides with arylboronic acids
Sabrina M. Nobre and Adriano L. Monteiro*
´
Group of Molecular Catalysis, Instituto de Quımica, UFRGS Av. Bento Gonc¸alves, 9500 Porto Alegre 91501-970, CP 15003 RS, Brazil
Received 24 August 2004; accepted 2 September 2004
Available online 21 September 2004
Abstract—A simple catalyst precursor prepared in situ from palladium acetate and triphenylphosphine shows high activity for the
Suzuki cross-coupling reaction of benzylic bromides and chlorides with aryl boronic acids. The reaction can be carried out at low
catalyst loading (0.002–1mol%) and under mild conditions (room temperature to 80ꢀC) furnishing diarylmethane derivatives in high
yields (86–99%).
ꢁ 2004 Elsevier Ltd. All rights reserved.
The palladium-catalyzed cross coupling of aryl halides
with arylboronic acids (Suzuki reaction) is a well estab-
boronic acids in acetone–water at room temperature.7
Over the last years, we have successfully applied Pd
and Ni based catalyst systems for the Suzuki reactions
of aryl halides and tosylates with arylboronic acids.8
More recently we have used a mixture of Pd(OAc)2
and PPh3 as a catalyst precursor in a successful homoge-
neous and recyclable Suzuki cross-coupling reaction,
and during these studies we have found that this system
is also active for the coupling of benzyl halides with aryl-
boronic acids.9 In this paper, we wish to report that a
simple system such as palladium acetate and triphenyl-
phosphine is able to perform the Suzuki cross-coupling
reaction of benzylic bromides and chlorides under mild
conditions and with low loadings of catalyst.10
lished and efficient method for the construction of Caryl
–
Caryl bonds and has found widespread use in organic
and polymer synthesis.1 Diarylmethane derivatives,
which are important building blocks in organic synthe-
sis, can also be obtained by a Suzuki reaction by using
benzyl halides in the place of aryl halides. For instance,
Suzuki reactions employing a benzyl halide have been
exploited to produce a macrobicycle and antagonists
of the human EP3 receptor2 and polybenzyls3. However,
compared with aryl halides, few examples exist in which
a benzylic halide is coupled under Suzuki conditions.
Most of the Suzuki coupling reactions of benzyl halides
were described with benylic bromides and Pd(PPh3)4 as
catalyst (3–10mol%).2–4 PdCl2(dppf) [dppf = 1,10-
bis(diphenylphosphino)ferrocene] was also used for the
Suzuki coupling reaction of cyclopropylboronic acids
and esters with benzyl bromide using Ag2O with KOH
as the base.5 Recently, it was reported that the tetrapo-
dal phosphine ligand tedicyp [cis,cis,cis-1,2,3,4-tetrakis
(diphenylphosphinomethyl) cylopentane] in conjunction
with [PdCl(C3H5)]2 is an efficient system for the coupling
of benzylic chlorides and bromides with arylboronic
acids.6 On the other hand phosphine-free oxime-derived
palladacycles were used as catalyst precursors for the
cross-coupling reaction of benzylic chlorides with aryl-
Pd(OAc)2 / PPh3
(0.002-1 mol%)
(HO)2B
X
+
R1
K3PO4 ; PhMe
25-80oC
R1
R2
R2
X = Cl and Br
A set of experiments was performed in order to establish
the best catalyst precursor, solvent, and base. Initially,
we investigated the coupling of benzyl bromide with
phenylboronic acids using different catalyst precursors
(palladacycle {PdCl[o-C6H4CH(Me)StBu]}2, Pd(OAc)2/
PPh3, NiCl2(PCy3)2, bases (K3PO4 and K2CO3), and
solvents (THF, toluene, and DMA) under reaction con-
ditions previously studied in our group.8,9 Although all
catalyst precursors gave the expected coupling product,
palladium acetate in the presence of triphenylphosphine
using toluene as solvent at 80ꢀC and K3PO4 as base was
Keywords: Benzylic halides; Suzuki cross-coupling reaction;
Diarylmethanes.
*
Corresponding author. Tel.: +55 51 33166303; fax: +55 51
0040-4039/$ - see front matter ꢁ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.020