Suzuki-Miyaura cross-coupling reaction catalyzed by PEPPSI-type 1,4-di(2,6-diisopropylphenyl)-1,2,3-triazol-5-ylidene (tzIPr) palladium complex

Article abstract of DOI:10.1002/ejoc.201201075

A 1,4-di(2,6-diisopropylphenyl)-1,2,3-triazol-5-ylidene (tzIPr)-based PEPPSI-type palladium complex was developed as an excellent precatalyst for the Suzuki-Miyaura cross-coupling reaction. The complex showed high activity under mild conditions for the cross-coupling reactions between various types of aryl chlorides and aryl boronic acids regardless of the steric and electronic nature of the substrates.

Full text of DOI:10.1002/ejoc.201201075

FULL PAPER
DOI: 10.1002/ejoc.201201075
Suzuki–Miyaura Cross-Coupling Reaction Catalyzed by PEPPSI-Type 1,4-
Di(2,6-diisopropylphenyl)-1,2,3-triazol-5-ylidene (tzIPr) Palladium Complex
Jie Huang,[a][‡] Jong-Tai Hong,[b,c][‡] and Soon Hyeok Hong*[b,c]
Keywords: Homogeneous catalysis / Palladium / C–C coupling / Cross-coupling / Carbene ligands / Biaryls
A
1,4-di(2,6-diisopropylphenyl)-1,2,3-triazol-5-ylidene
under mild conditions for the cross-coupling reactions be-
tween various types of aryl chlorides and aryl boronic acids
regardless of the steric and electronic nature of the sub-
strates.
(tzIPr)-based PEPPSI-type palladium complex was devel-
oped as an excellent precatalyst for the Suzuki–Miyaura
cross-coupling reaction. The complex showed high activity
veloping better Pd catalysts using the tzNHC ligands. While
preparing this manuscript, Fukuzawa and co-workers re-
ported the synthetic, structural, and catalytic studies of allyl
tzNHC Pd complexes.[9] In addition, Albrecht and co-
workers recently reported tzNHC-based PEPPSI (PEPPSI
= pyridine-enhanced precatalyst preparation, stabilization,
and initiation, Figure 1) type Pd complexes,[12] in which ap-
pended groups of tzNHC are Me, nBu, Ph, or Mes
groups.[10] We have also investigated the possibility of using
tzNHC for Pd-catalysis using more bulky 1,4-di(2,6-diisop-
ropylphenyl)-1,2,3-triazol-5-ylidene (tzIPr), because it has
been well-documented that ligands with increased steric
bulk are more efficient in Pd-catalyzed Suzuki–Miyaura re-
actions.[11] Herein, we report our study on the synthesis and
catalytic activity of a tzIPr-based PEPPSI-type Pd complex
for Suzuki–Miyaura cross-coupling reactions.
Introduction
The transition-metal-catalyzed Suzuki–Miyaura cross-
coupling reaction is one of the most widely used methods
for forming carbon–carbon bonds.[1] A wide variety of or-
ganic compounds including polymers,[2] pharmaceuticals,[3]
and natural products,[4] can be synthesized by applying this
reaction. N-Heterocyclic carbenes (NHCs) have become
popular ligands for the Pd-catalyzed Suzuki–Miyaura cou-
pling reactions.[5] The NHCs are stronger neutral σ-donors
and less oxidation-sensitive than tertiary phosphanes. Our
group has recently reported that a more σ-donating C4 or
C5 binding abnormal NHC, derived from C2-protected
imidazolium salts, could be a better ligand than traditional
NHC ligands in Pd-catalyzed Suzuki–Miyaura reactions.[6]
To develop more versatile and active NHC ligands for C–C
bond formation, we have investigated other types of NHC
ligands. Among the various types of NHCs, those derived
from substituted 1,2,3-trazolin-5-ylidene (tzNHC), first re-
ported by Albrecht and co-workers, have recently been de-
veloped as promising ligands for homogeneous catalysis.[7]
tzNHC precursors can be readily prepared by the [3+2] cy-
cloaddition of an alkyne with an azide.[8]
To find a more active and versatile catalyst for the
Suzuki–Miyaura reactions, we have been interested in de-
Figure 1. Structure of NHC-based PEPPSI-type Pd complexes de-
veloped by Organ.
[a] Division of Chemistry and Biological Chemistry, School of
Physical and Mathematical Sciences, Nanyang Technological
University,
Singapore 637371, Singapore
Results and Discussion
[b] Department of Chemistry, College of Natural Sciences, Seoul
National University,
The tzIPr-palladium complexes were conveniently syn-
thesized by transmetallation from a silver carbene com-
plex.[9a,10] A triazolium salt 2 was treated with silver oxide
in dichloromethane at 35 °C for 16 h to generate the silver
carbene complex 3 (Scheme 1). The crude silver carbene
complex 3 was immediately used for the synthesis of palla-
dium complex 4. After treating 3 with [PdCl2(CH3CN)2],
Seoul 151-747, Republic of Korea
Fax: +82-2-889-1568
E-mail: soonhong@snu.ac.kr
Homepage: http://sites.google.com/site/hongshsnuchem/
[c] Korea Carbon Capture & Sequestration R&D Center,
Daejeon 305-303, Republic of Korea
[‡] These authors contributed equally to this work.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201075.
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Eur. J. Org. Chem. 2012, 6630–6635

Precatalyst for the Suzuki–Miyaura Cross-Coupling Reaction
Scheme 1. Syntheses of tzNHC-Pd complexes.
dimeric Pd complex 4 was isolated as a yellow solid in 50%
The Pd–C(NHC center) bond lengths in tzIPr Pd com-
yield. Complexes 5 and 6 were synthesized by treating 4 plexes 4 and 5 are 1.961 and 1.965 Å, respectively
with 3-chloropyridine and 1-methylimidazole, respectively. (Table 1).[14] These Pd–C(NHC center) bond lengths are in
The structures of 4 and 5 were confirmed by X-ray crystal- the same range as those of the reported tzNHC-Pd com-
lographic analysis as well as by NMR spectroscopy (Fig- plexes.[9a,10] The bond lengths are also similar to those of
ure 2).[13] Unfortunately, no suitable crystals of complex 6 traditional NHC-based Pd PEPPSI complexes. For exam-
for X-ray crystallographic analysis were obtained; this com- ple, in the case of trans-dichloro[1,3-bis(2,6-diisoprop-
plex was therefore characterized by NMR and mass analy- ylphenyl)imidazolylidinium](3-chloropyridine) (1a), the
ses.
length of Pd–C is 1.969(3) Å.[12d] It has been reported that
Figure 2. Crystal structure of 4 and 5 with thermal ellipsoids drawn at the 30% probability level.
Eur. J. Org. Chem. 2012, 6630–6635
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J. Huang, J.-T. Hong, S. H. Hong
FULL PAPER
M–Ccarbene bond lengths are not so sensitive to small Table 3. Screening for biaryl synthesis using complex 5.[a]
changes in bond order.[6] The Pd–Npy bond length of
2.089(2) Å of 5 was shorter than that of 1a (2.137(2) Å).[12d]
In the case of [(η3-allyl)(tzIPr)Pd] and [(η3-allyl)(IPr)Pd]
complexes, the Pd–C(3) bond lengths [2.201(3) and 2.210(6)
Å, respectively] are similar, leading Fukuzawa and co-
Entry
Base
Solvent
Yield [%][b]
workers to suggest similar trans influence of tzIPr and IPr
ligands in [(η3-allyl)(NHC)Pd] complexes.[9a] In our case,
the significantly shorter Pd–N bond length of 5 may indi-
cate less trans influence of tzIPr than IPr. The triazole tor-
sional angles are 4–8°, indicating that the triazole rings are
planar and in an aromatic system.
1
2
3
4
5
6
7
8
9
tBuOK
K2CO3
Cs2CO3
K3PO4
NaOMe
CsF
tBuOK
tBuOK
tBuOK
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
1,4-dioxane
toluene
tBuOH
95
24
16
87
51
43
trace
trace
trace
Table 1. Selected bond lengths [Å] and angles [°] of 4 and 5.
4
5
[a] Reaction conditions: ArCl (0.5 mmol), boronic acid (1.1 equiv.),
solvent (1.0 mL/mmol halide). [b] GC yield using dodecane as in-
ternal standard.
Pd(1)–C(1)
Pd(1)–Cl(2)
Pd(1)–Cl(4)
1.961(10)
2.3002(7)
2.321(3)
Pd(1)–C(7)
Pd(1)–Cl(1)
Pd(1)–Cl(2)
1.965(2)
2.3002(7)
2.2964(7)
C(1)–Pd(1)–Cl(1) 90.4(3)
C(1)–Pd(1)–Cl(4) 92.4(3)
Cl(1)–Pd(1)–Cl(4) 173.96(11)
C(7)–Pd(1)–Cl(1) 91.43(7)
C(7)–Pd(1)–Cl(2) 88.71(7)
Cl(2)–Pd(1)–Cl(1) 178.77(3)
to generate ortho-substituted biaryls under mild conditions.
Cross-coupling products from ortho-disubstituted 1-chloro-
2,6-dimethylbenzene (7a) and para-substituted phenyl-
boronic acids were obtained in high yields (Table 4, entries
2–4). The 1-chloro-2,6-dimethylbenzene coupled with more
sterically congested ortho-substituted phenylboronic acids
to give the corresponding biaryls with good yields (Table 4,
entries 5 and 6). Moreover, the reaction of 7a with 1-
naphthylboronic acid 8g gave the coupling product 9g in
73% yield (Table 4, entry 7). Functional group tolerance
was also good. 2-Thienylboronic acid 8h with 7a gave the
corresponding product 9h in 85% yield (Table 4, entry 8).
The cross-coupling reaction of 8i, which possesses a
hydroxyl group, proceeded smoothly to afford the desired
product in 92% yield (Table 4, entry 9). Both electron-rich
and electron-poor aryl chlorides worked effectively as cross-
coupling partners, giving excellent yields of the correspond-
ing product (Table 4, entries 10–12). Even with 1,2-dichloro-
benzene, containing two C–Cl bonds, the doubly cross-
coupled product 9m was obtained with 55% yield (Table 4,
entry 13). The challenging reaction of highly hindered sub-
strates of 7a and 8j worked smoothly to give the coupling
product 9n in 82% yield with an increased reaction time of
24 h at an elevated temperature of 110 °C (Table 4, en-
try 14). Compared with the activity of IPr-based PEPPSI-
type catalyst 1a, with similar steric hindrance around the
Pd center,[12d,12f] complex 5 exhibited better activity for the
Suzuki–Miyaura reactions with aryl chlorides and for syn-
thesis of sterically bulky biaryls. Organ and co-workers de-
veloped complex 1b, which exhibits excellent activities for
cross-coupling reactions, by increasing the steric bulk of the
NHC ligand.[12f] Albrecht and co-workers showed that, in
contrast to the homogeneous catalysis observed with the
N(3)–C(1)–C(2)
N(1)–N(2)–N(3)
N(2)–N(3)–C(7)
104.0(9)
103.6(7)
114.3(8)
N(3)–C(7)–C(8)
N(1)–N(2)–N(3)
N(2)–N(3)–C(1)
103.2(3)
102.2(4)
114.4(4)
Catalytic activities for the Suzuki–Miyaura reactions
were screened with complexes 4–6 (Table 2), and 1-chloro-
2,6-dimethylbenzene and boronic acid were selected as a
model reaction. The reaction conditions were optimized
and tBuOK and EtOH were identified as the best base and
solvent, respectively (Table 3). Complexes 4 and 5 showed
excellent activities in the cross-coupling reaction at room
temperature. Complex 6 with 1-methylimidazole as a ligand
showed slightly reduced activity, presumably due to slower
dissociation of the imidazole ligand than pyridine.[15]
Table 2. Activity of NHC-Pd complexes for the Suzuki–Miyaura
reaction.[a]
Entry
Pd com-
plex
Catalyst load- Time [h][b] Yield [%][c]
ing [mol-%]
1
2
3
4
5
5
5
5
4
6
1.0
0.5
0.1
0.5
0.5
2
2
5
2
5
91
89
80
88
70
[a] Reaction conditions: 1-chloro-2,6-dimethylbenzene (1.0 mmol),
boronic acid (1.1 equiv.), ethanol (1.0 mL/mmol halide). [b] Reac-
tion progress was monitored by TLC analysis. [c] Isolated yield.
The scope of the Suzuki–Miyaura reactions catalyzed by original PEPPSI systems, triazolylidene-based PEPPSI-type
5 was evaluated (Table 4). Complex 5 exhibited good to ex- Pd complexes undergo a heterogenization process that gen-
cellent activities with various substrates at ambient tem- erates palladium nanoparticles as the resting state of the
perature. Ortho-substituted biaryls are important structural catalyst.[10] Further catalyst development is in progress
motifs, and they are found in many biologically active com- based on further increasing the steric bulk of the tzNHC
pounds and organic materials.[16] Complex 5 performed well ligands.
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Eur. J. Org. Chem. 2012, 6630–6635

Precatalyst for the Suzuki–Miyaura Cross-Coupling Reaction
Table 4. Suzuki–Miyaura reactions catalyzed by complex 5.[a]
Conclusions
We have developed a tzNHC-based PEPPSI-type Pd
complex as an excellent precatalyst for the Suzuki–Miyaura
cross-coupling reaction. The complex showed high activity
under mild conditions for the cross-coupling reactions be-
tween various types of aryl chlorides and aryl boronic acids
regardless of the steric and electronic nature of the sub-
strates.
Experimental Section
General Considerations: All reactions were carried out in oven-dried
glassware under an inert atmosphere of dry argon or nitrogen. All
reagents were purchased from Aldrich or Alfa Aesar and used as
received. Analytical TLC was performed with Merck 60 F254 silica
gel (0.25 mm thickness). Column chromatography was performed
with Merck 60 silica gel (230–400 mesh). NMR spectra were re-
corded with a Bruker 300 MHz or a Bruker 400 MHz spectrometer.
Tetramethylsilane was used as reference, the chemical shifts are re-
ported in ppm, and the coupling constants in Hz. GC yields were
obtained with an Agilent 7890A instrument equipped with an HP-
5 column using dodecane as internal standard. Ligand 2 was syn-
thesized as summarized in Scheme 2 and described below.
Scheme 2. Syntheses of 1,4-di(2,6-diisopropylphenyl)-1,2,3-triazol-
ium iodide (2).
1-Azido-2,6-diisopropylbenzene:[17] To a solution of 2,6-diisoprop-
ylaniline (1.773 g, 10.0 mmol) in 10% HCl (15 mL), a solution of
NaNO2 (0.690 g, 10.0 mmol) in water (3 mL) was added at 0–5 °C
with vigorous stirring. The mixture was kept below 5 °C for 30 min,
then a solution of NaN3 (0.72 g, 11.0 mmol) in water (15 mL) was
added dropwise while the temperature was maintained below 5 °C.
After stirring for 3 h, the mixture was warmed to room temp. and
poured into saturated aqueous NaHCO3 (50 mL). After extraction
with EtOAc (50 mL), the organic layer was washed with brine
(50 mL), dried with Na2SO4, and concentrated in vacuo. The resi-
[a] Reaction conditions: ArCl (1.0 mmol), boronic acid (1.1 equiv.),
complex 5 (0.5 mol-%), ethanol (1.0 mL/mmol ArCl). [b] Reaction
time was determined by monitoring the reaction by TLC. [c] Iso-
lated yield; average of at least two runs. [d] Yield was determined
by H NMR analysis due to contamination by a small amount of
inseparable byproduct derived from homocoupling of boronic ac-
ids. [e] 1.5 equiv. of boronic acid used. [f] Reaction conditions: ArCl
1
(0.5 mmol), boronic acid (3.0 equiv.),
(2.0 equiv.). [g] Reaction conditions: ArCl (0.5 mmol), boronic acid
5 (1.0 mol-%), tBuOK
(1.1 equiv.), 1,4-dioxane (1.0 mL/mmol ArCl), 5 (5 mol-%), 110 °C.
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J. Huang, J.-T. Hong, S. H. Hong
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due was purified by flash silica gel column chromatography to give
the product (1.015 g, 50%).
1123.3110; found 1123.3115. C54H74Cl4N6Pd2 (1161.83): calcd. C
55.82, H 6.42, N 7.23; found C 55.61, H 6.15, N 6.99.
1-Iodo-2,6-diisopropylbenzene:[18] To a solution of 2,6-diisoprop-
ylaniline (1.773 g, 10.0 mmol) in acetone (15 mL), 10% HCl
(15 mL) was added at room temperature. The resulting solution
was cooled to 0 °C, and a solution of NaNO2 (0.91 g, 13.0 mmol)
in H2O (3 mL) was added dropwise. The reaction mixture was
stirred at 0 °C for 1 h, then a solution of KI (4.98 g, 30.0 mmol) in
H2O (10 mL) was added. After 6 h, the solution was extracted with
Et2O (3ϫ50 mL) and the combined ether layers were washed with
brine, dried, and concentrated. The residue was purified by flash
silica gel column chromatography to afford 1-iodo-2,6-diisoprop-
ylbenzene (1.152 g, 40%).
1-Ethynyl-2,6-diisopropylbenzene:[19] Under an Ar atmosphere, a
50 mL Schlenk flask was charged with 1-iodo-2,6-diisopropylbenz-
ene (576 mg, 2 mmol), HCϵCZnBr [3 mmol; prepared from
HCϵCMgBr (0.5 m in THF, 3 mmol, 6 mL) and anhydrous ZnBr2
(675 mg, 3 mmol) dissolved in THF (5 mL)], [Pd(PPh3)4] (115 mg,
0.1 mmol), and DMF (2 mL). The mixture was stirred for 18 h at
60 °C, then the reaction mixture was quenched with aqueous NaCl,
extracted with Et2O, dried with Na2SO4, and concentrated in
vacuo. The product (141 mg, 38%) was separated by column
chromatography using hexane as eluent.
Complex 5: Under an Ar atmosphere, a Schlenk flask was charged
with 3-chloropyridine (41 mg, 0.36 mmol), 4 (209 mg, 0.18 mmol),
and CH2Cl2 (1 mL). The reaction mixture was stirred for 3 h at
35 °C. After evaporation of all volatiles, the residue was washed
with pentane and complex 5 was obtained. Yield: 247 mg (99%);
yellow solid. 1H NMR (400 MHz, CDCl3): δ = 1.10 (d, J = 7.2 Hz,
6 H, ArCHCH3CH3), 1.13 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3),
1.46 (d, J = 6.4 Hz, 12 H, ArCHCH3CH3), 2.96–3.07 (m, 4 H,
ArCHCH3CH3), 3.84 (s, 3 H, N-CH3), 7.08 (dd, J = 5.6, 8.0 Hz, 1
H, HPy), 7.36 (d, J = 4.8 Hz, 2 H, HAr), 7.38 (d, J = 4.4 Hz, 2 H,
HAr), 7.52–7.56 (m, 3 H, HAr/Py), 8.63 (dd, J = 1.2, 5.6 Hz, 1 H,
HPy), 8.71 (d, J = 2.0 Hz, 1 H, HPy) ppm. 13C NMR (100 Hz,
CDCl3):
δ
=
d
22.8, 24.6, 25.0, 25.8, 29.1, 31.0
(ArCHCH3CH3 ϫ6), 37.4 (NCH3), 123.1 (CAr), 123.9 (CAr), 124.0
(CPy), 124.3 (CAr), 131.1 (CAr), 132.0 (Ctz-Pd), 135.6 (CPy), 137.3
(CPy), 142.6 (CAr), 146.3 (CAr), 149.5 (Ctz-Ipr), 150.3 (CPy), 150.5
(CPy) ppm. HRMS: m/z calcd. for C32H41N4Cl2Pd [M – Cl]+
657.1743; found 657.1744. C32H41Cl3N4Pd (694.46): calcd. C 55.34,
H 5.95, N 8.07; found C 55.08, H 5.85, N 7.75.
Complex 6: Under an Ar atmosphere, a Schlenk flask was charged
with 1-methylimidazole (7.1 mg, 0.086 mmol),
4
(50 mg,
0.043 mmol), and CH2Cl2 (0.5 mL). The reaction mixture was
stirred for 3 h at 35 °C. The solvent was removed under vacuo, and
the residue was purified by a flash chromatography on silica gel
using CH2Cl2 as eluent. Yield: 34 mg (60%); yellow solid. 1H NMR
(400 MHz, CDCl3): δ = 1.08 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3),
1.11 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3), 1.45 (d, J = 6.4 Hz, 12
H, ArCHCH3CH3), 3.00–3.07 (m, 4 H, ArCHCH3CH3), 3.46 (s, 3
H, NIm-CH3), 3.81 (s, 3 H, N-CH3), 6.55 (dd, J = 2.0, 4.0 Hz, HIm),
7.25 (dd, J = 1.8, 3.4 Hz, HIm), 7.33 (d, J = 4.0 Hz, 2 H), 7.33 (d,
J = 4.4 Hz, 2 H), 7.48–7.53 (m, 2 H), 7.76 (s, 1 H, HIm) ppm.
13C NMR (100 Hz, CDCl3): δ = 22.9, 24.6, 25.0, 25.8, 29.0, 30.9
(ArCHCH3CH3 ϫ6), 34.0 (NImCH3), 37.2 (NCH3), 119.0 (CAr),
123.6 (CAr), 123.8 (CAr), 123.9 (CAr), 128.6 (CAr), 131.1 (Ctz-Pd),
136.2 (CIm), 138.5 (CIm), 142.1 (CAr), 145.2 (CAr), 146.4 (CIm),
150.3 (Ctz-IPr) ppm. HRMS: m/z calcd. for C31H43N5ClPd [M –
Cl]+ 626.2242; found 626.2244. C31H43Cl2N5Pd (663.02): calcd. C
56.16, H 6.54, N 10.56; found C 55.93, H 6.35, N 10.33.
1,4-Di(2,6-diisopropylphenyl)-1,2,3-triazole:[20] In a tube with a
screw-cap, 1-azido-2,6-diisopropylbenzene (270 mg, 1.33 mmol), 1-
iodo-2,6-diisopropylbenzene (225 mg, 1.21 mmol), and [(SIMes)-
CuBr] (29 mg, 5 mol-%) were loaded. The reaction was heated at
70 °C. After 18 h, the liquid (starting material) became solid (target
product), and was dissolved with EtOAc, and concentrated in
vacuo. The product (336.9 mg, 71%) was separated by column
chromatography (hexane/ethyl acetate, 15:1).
1,4-Di(2,6-diisopropylphenyl)-1,2,3-triazolium Iodide (2):[9a] Triazole
1 (140 mg, 0.36 mmol) was added to acetonitrile (1 mL) and methyl
iodide (511 mg, 3.6 mmol) and the reaction mixture was heated at
60 °C for 24 h. Solvent was removed under vacuo and the solid
residue was recrystallized (CH2Cl2/hexane); yield 169 mg (88%);
yellow solid. 1H NMR (400 MHz, CDCl3): δ = 1.17 (d, J = 6.8 Hz,
6 H, ArCHCH3CH3), 1.27 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3),
1.30 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3), 1.33 (d, J = 6.8 Hz, 6
H, ArCHCH3CH3), 2.34–2.42 (m, 4 H, ArCHCH3CH3), 4.36 (s, 3
H, N-CH3), 7.39 (d, J = 5.8 Hz, 2 H, ArH), 7.41 (d, J = 5.8 Hz, 2
H, ArH), 7.63–7.68 (m, 2 H, ArH), 9.29 (s, 1 H, Htz) ppm. 13C
NMR (100 Hz, CDCl3): δ = 23.2, 23.8, 24.4, 25.1, 29.2, 32.0
(ArCHCH3CH3 ϫ6), 40.2 (NCH3), 117.1 (CAr), 124.3 (CAr), 124.9
(CAr), 130.6 (Ctz-H), 133.2 (CAr), 133.4 (CAr), 142.0 (CAr), 145.0
(CAr), 148.8 (Ctz-Ipr) ppm.
Typical Procedure for 9a: A Schlenk flask was charged with 1-
chloro-2,6-dimethylbenzene (70 mg, 0.5 mmol), boronic acid
(67 mg, 0.55 mmol), tBuOK (84 mg, 0.75 mmol), complex
5
(17 mg, 0.025 mmol), and EtOH (0.5 mL) under Ar. The mixture
was stirred at room temperature and, after the completion of the
reaction (monitored by TLC), the reaction mixture was poured into
saturated aqueous NaCl and extracted with CH2Cl2 (3ϫ10 mL).
The combined organic extracts were washed with saturated aque-
ous NaCl (3ϫ10 mL), dried with Na2SO4, filtered, and concen-
trated in vacuo. Purification was carried out by flash silica gel
chromatography (hexane) to give product 9a (162 mg, 89%) as a
colorless liquid. Characterization data of all of the biaryl products
have been previously reported, and the identities of 9a–n were con-
Complex 4: To a solution of 2 (749 mg, 1.41 mmol) in CH2Cl2
(20 mL), Ag2O (326 mg, 1.41 mmol) was added. The mixture was
stirred at 35 °C for 16 h in the dark, and filtered through Celite.
[Pd(CH3CN)2Cl2] (730 mg, 2.82 mmol) was added and, after stir-
ring for 5 h at 35 °C, the product was separated by column
chromatography (CH2Cl2); yield 410 mg (50%); yellow solid. 1H
NMR (400 MHz, CDCl3): δ = 0.99 (d, J = 7.6 Hz, 6 H,
ArCHCH3CH3), 1.02 (d, J = 6.8 Hz, 6 H, ArCHCH3CH3), 1.46
(d, J = 6.4 Hz, 6 H, ArCHCH3CH3), 1.27–1.30 (m, 6 H,
ArCHCH3CH3), 2.57–2.62 (m, 2 H, ArCHCH3CH3), 2.63–2.71 (m,
2 H, ArCHCH3CH3), 3.73 (s, 3 H, N-CH3), 7.31 (d, J = 8.0 Hz, 4
H, HAr), 7.57 (dd, J = 7.6, 15.2 Hz, 2 H, HAr) ppm. 13C NMR
1
firmed by H NMR spectroscopic data comparison.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra of Pd complexes, and
1H NMR spectra of biaryls 9.
(100 Hz, CDCl3):
(ArCHCH3CH3 ϫ6), 37.3 (NCH3), 122.4 (CAr), 124.0 (CAr), 131.1
δ = 22.8, 24.6, 25.0, 25.8, 29.0, 31.0
Acknowledgments
(Ctz-Pd), 135.0 (CAr), 138.1 (CAr), 142.0 (CAr), 146.2 (CAr), 150.2 This work was supported by the Korea CCS R&D Center (KCRC)
(Ctz-Ipr) ppm. HRMS: m/z calcd. for C54H74N6Cl3Pd2 [M – Cl]+
(grant number 2012-0008944) funded by the Korea Government,
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Eur. J. Org. Chem. 2012, 6630–6635

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Received: August 8, 2012
Published Online: October 11, 2012
Eur. J. Org. Chem. 2012, 6630–6635
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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