Communications
electronic effects of the ligand framework can be simply
with methanesulfonyl chloride) was examined using the
preliminary optimized reaction conditions (Table 2). In gen-
eral, complete conversion was detected within 3 h when
2 mol% of Pd were used. No homocoupled side-products
were detected by GC-MS analysis. Notably, the coupling of
unactivated aryl mesylates was achieved with 0.5 mol% of Pd
(Table 2, entry 2). A variety of common functional groups
were compatible under these mild reaction conditions,
including keto, aldehyde, ester, and nitrile (Table 2,
entries 6–12). Moreover, deactivated p-methoxyphenyl mesy-
late was discovered to be a feasible coupling partner in this
reaction (Table 2, entry 14).
Besides functionalized aryl mesylates, the scope of the Pd/
L2 catalytic system can be extended to heteroaryl mesylates
(Table 3). Sterically congested arylboronic acids were effi-
ciently coupled with quinolyl mesylate in excellent yields
(Table 3, entries 1–3). Particularly noteworthy was that the
extremely hindered 2,4-di-tert-butyl-6-methoxyphenylbor-
onic acid was found to be a capable coupling partner in this
reaction (Table 3, entry 3). Benzothiazolyl and pyridyl mesy-
lates can be coupled with arylboronic acids to afford the
corresponding desired product in good yields (Table 3,
entries 4–6).
modified by a random matching of arylhydrazines and
substituted acetophenones (Scheme 1). Moreover, ligands
L1–L3 can be directly purified by a single crystallization and
are highly air-stable in both solid and solution states.[16]
Palladium-catalyzed Suzuki–Miyaura couplings of unac-
tivated aryl mesylates have, to date, not been reported. This
area remains highly challenging, as aryl mesylate electro-
philes are proposed to be less susceptible to oxidative
addition than the corresponding aryl arenesulfonates.[9] In
addition, the reactivity of aryl mesylates (ArOMs) was at least
fivefold lower in general than the corresponding aryl tosylates
(ArOTs) under the same reaction conditions.[17] With a series
of indolylphosphane ligands, the feasibility on Suzuki-type
couplings of aryl mesylates was investigated. Electronically
neutral 4-tert-butylphenyl mesylate and 4-tolylboronic acid
were used as the prototypical substrates in our reaction
(Table 1). Ligand L1 (with a diphenylphosphano moiety)
Table 1: Initial screening of Suzuki–Miyaura coupling of unactivated
ArOMs.[a]
In addition to arylboronic acids, which are widely used as
coupling partners in Suzuki–Miyaura reactions, other boronic
acid surrogates are highly attractive.[18] The new palladium
catalyst system demonstrated the versatility of aryl mesylates
in Suzuki-type coupling reactions using other organoboron
nucleophiles. Aryl trifluoroborate salts and a pinacol boro-
nate ester were successfully coupled in good yields with aryl
mesylates using the Pd/L2 catalytic system (Scheme 2).
Within the past decade, isolated palladium precatalysts
have received increasing levels of attention.[19] In addition to
their convenience in handling, they display comparative (or
sometimes even greater) activity with respect to in situ
generated catalysts in cross-coupling reactions. We applied
the isolated dimeric palladacyclic complex to the Suzuki–
Miyaura coupling of aryl mesylates (Scheme 3). This air-
stable palladium complex 5 with twice the amount of addi-
tional L2 displayed essentially the same reactivity as in the
in situ generated catalyst (Scheme 3 vs. Table 1, entry 2).
In conclusion, we have succeeded in showing the first
Suzuki–Miyaura coupling of unactivated aryl mesylates. The
Pd/L2 catalyst system is active with a range of mesylate
substrates with various common functional groups. Moreover,
the scope of the organoboron nucleophile can be extended
beyonded boronic acids to aryltrifluoroborate salts and
boronate esters. In view of the simplicity of the ligand
synthesis as well as the easy modification of the ligand
skeleton, we anticipate that further enhancements in reac-
tivity and versatility of the ligand series will be attainable.
Entry
Ligand
Solvent
Base
Yield [%][b]
1
2
3
4
5
6
7
8
9
L1
L2
L3
none
L2
L2
L2
L2
L2
L2
L2
L2
tBuOH
tBuOH
tBuOH
tBuOH
toluene
DMF
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
Cs2CO3
K2CO3
KOtBu
CsF
K3PO4
<1
89
84
<1
42
50
33
83
79
<1
93
THF
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
10
11
12
97
[a] Reaction conditions: ArOMs (1.0 mmol), Ar’B(OH)2 (2.0 mmol),
base (3.0 mmol), Pd(OAc)2 (2 mol%), ligand (L1–L3; 0.04 mmol),
solvent (3.0 mL), at 1108C under N2 for 4 h (see Supporting Information
for experimental details). [b] Yields were calculated using calibrated GC
with dodecane as the internal standard. tol=p-tolyl.
apparently provided no conversion. However, the dicyclo-
hexylphosphano L2 and diisopropylphosphano L3 analogues
showed good to excellent catalytic activity (Table 1, entries 1–
3). Among the solvents surveyed (tBuOH, toluene, DMF, and
THF), tBuOH provided the best product yield (Table 1,
entries 2 and 5–7). Screening of commonly used inorganic
bases indicated that CsF and K3PO4 were suitable bases for
the aryl mesylate coupling reaction (Table 1, entries 11 and
12). When potassium tert-butoxide was applied as a base in
this reaction, a significant amount of phenolic side products
(from the hydrolysis of sulfonate) were formed (Table 1,
entry 10).
Received: July 2, 2008
Published online: September 11, 2008
To test the effectiveness of the Pd/L2 catalytic system, a
range of aryl mesylates (prepared from substituted phenols
Keywords: cross-coupling · homogeneous catalysis · mesylates ·
palladium · phosphanes
.
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 8059 –8063