A triarylphosphine ligand bearing dodeca(ethylene glycol) chains: Enhanced efficiency in the palladium-catalyzed suzuki-miyaura coupling reaction

Article abstract of DOI:10.1021/ol900578g

A new phosphine bearing dodeca(ethylene glycol) chains has been synthesized and employed as a ligand in the palladium-catalyzed Suzuki-Miyaura coupling reaction. The system was found to be highly effective using unactivated aryl chlorides as the substrate.

Full text of DOI:10.1021/ol900578g

ORGANIC
LETTERS
2
009
Vol. 11, No. 10
121-2124
A Triarylphosphine Ligand Bearing
Dodeca(ethylene glycol) Chains:
Enhanced Efficiency in the
2
Palladium-Catalyzed Suzuki-Miyaura
Coupling Reaction
Tetsuaki Fujihara, Shohei Yoshida, Jun Terao, and Yasushi Tsuji*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto UniVersity, Kyoto 615-8510, Japan
ytsuji@scl.kyoto-u.ac.jp
Received March 25, 2009
ABSTRACT
A new phosphine bearing dodeca(ethylene glycol) chains has been synthesized and employed as a ligand in the palladium-catalyzed
Suzuki-Miyaura coupling reaction. The system was found to be highly effective using unactivated aryl chlorides as the substrate.
1
Phosphines are one of the most important ligands for
homogeneous transition-metal-catalyzed reactions realizing
high efficiency. Therefore, a wide variety of phosphines
Scheme 1
2
have been designed to realize high catalytic activity and
selectivity. Recently, we designed and prepared triarylphos-
phines (1 and 2 in Scheme 1), in which tetra(ethylene glycol)
3
4
(
EG4, M
w
3
) 191) chains are connected onto the PPh core.
(
1) (a) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47,
6
1
338–6361. (b) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41,
461–1473. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H.
Although EG4 moieties are easy to manipulate, the EG4
Acc. Chem. Res. 2001, 34, 895–904. (d) Homogeneous Catalysis with Metal
Phosphine Complexes; Pignolet, L. H., Ed.; Plenum: New York, 1983.
chain is not long enough and 1 has only limited efficiency
(
2) (a) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D. Applications
5
as a ligand in the Suzuki-Miyaura coupling reaction of
of Transition Metal Catalysts in Organic Synthesis; Springer, Berlin, 1999.
b) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principle
6
unactivated aryl chlorides. In order to realize highly efficient
(
and Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, 1987. (c) Homogeneous Transition Metal Catalyzed
Reaction; Moser, W. R., Slocum, D. W., Eds.; American Chemical Society:
Washington, DC, 1992.
ligands, EG4 chains must be arranged dendritically at the
periphery of the ligand (2) via lengthy multistep synthesis.
In this paper, we wish to report that a dodeca(ethylene glycol)
4
10.1021/ol900578g CCC: $40.75
Published on Web 04/17/2009
 2009 American Chemical Society

(
w
EG12, M ) ca. 540) chain is a suitable moiety to enhance
efficiency of the ligand without such an elaborated dendritic
structure of 2. While much longer poly(ethylene glycol)
(
PEG, mainly M ) 2000-6000) chains are often employed
w
7
for preparation of water-soluble ligands, we successfully
utilized a relatively short EG12 chain to enhance the
efficiency of a ligand in an organic solvent.
The phosphine 3 was prepared straightforwardly in good
yields from commercially available EG12 monomethyl ether
(
2 2 n
5, HO(CH CH O) Me, n ) 12 on average) as shown in
4
,8
Scheme 2 (for details, see Supporting Information). The
Scheme 2
Figure 1. MALDI-TOF mass spectra of (a) 3 and (b) 5.
31
not affected by a solvent, and P resonances appear at -9.22
ppm in CDCl and -9.39 ppm in THF-d . The basicity of 3
can be evaluated by P-Se coupling constants of the
corresponding phosphine selenide SedPR
3
8
1
J
9
3
. The coupl-
ing constant (hence basicity) of 3 (715 Hz) is very similar
4
and comparable to those of 1 (714 Hz), 2 (715 Hz), and
PPh
PPh
3
(730 Hz). Thus, the EG12 chains introduced on the
core do not affect the electronic property of the
3
phosphine. These triarylphosphines are much weaker base
1
than P(t-Bu) ( JP-Se ) 686 Hz) and tricyclohexylphos-
3
1
phine ( JP-Se ) 674 Hz).
The phosphine 3 was employed as a ligand in the
Suzuki-Miyaura coupling reaction of 4-chlorotoluene with
phenylboronic acid in the presence of a catalytic amount of
2 2 2 3
[PdCl (PhCN) ] with K CO in THF at 60 °C (Table 1). As
Table 1. Effect of a Phosphine and Relevant Ligand Systems on
a
the Coupling Reaction
MALDI-TOF mass spectrum of 3 shows the molecular ion
+
peaks centered at m/z ) 5632 ([M] + Na ) with the constant
b
entry
added ligand
yield (%)
peak interval of 44 (Figure 1a). From the spectrum, the M
was calculated to be 1.001, and the value is consistent
with the M /M ) 1.028 of 5 (Figure 1b). These results
clearly indicated that the nine EG12 chains are successfully
w
/
M
n
1
2
3
4
5
6
1
3
53
92(88)
0
0
0
0
w
n
PPh
PPh
PPh
PPh
3
3
3
3
c
31
1
+ 5-Me
incorporated onto 3. P{ H} NMR spectra of 3 are virtually
d
+ 7
e
+ 4
(
3) For ligands with tetra(ethylene glycol) moiety, see: (a) Ohta, H.;
a
Fujihara, T.; Tsuji, Y. Dalton Trans. 2008, 37, 9–385. (b) Fujita, K.-I.;
Kujime, M.; Muraki, T. Bull. Chem. Soc. Jpn. 2009, 82, 261–266. (c)
Muraki, T.; Fujita, K.-I.; Kujime, M. J. Org. Chem. 2007, 72, 7863–7870.
4-Chlorotoluene (2.0 mmol), phenylboronic acid (4.0 mmol),
(PhCN) ] (0.010 mmol, 0.50 mol %), phosphine (0.020 mmol, P/Pd
CO (4.0 mmol) in THF (1.0 mL) at 60 °C for 20 h. Yield
[PdCl
2
2
b
) 2), and K
2
3
(
d) Muraki, T.; Fujita, K.-I.; Terakado, D. Synlett 2006, 264, 6–2648. (e)
based on the GC internal standard technique. The data in parentheses shows
c
d
Hoen, R.; Leleu, S.; Botman, P. N. M.; Appelman, V. A. M.; Feringa, B. L.;
yield of the isolated product. Molar ratio of 5-Me/PPh
3
) 9. Molar ratio
e
Hiemstra, H.; Minnaard, A. J.; van Maarseveen, J. H. Org. Biomol. Chem.
of 7/PPh
3
) 3. Molar ratio of 4/PPh
3
) 1.
2
006, 4, 613–615.
4) Fujihara, T.; Yoshida, S.; Ohta, H.; Tsuji, Y. Angew. Chem., Int.
Ed. 2008, 47, 8310–8314.
5) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457–2483. (b)
(
(
reported previously, 1 was not so efficient as a ligand and
-phenyltoluene was afforded in 36% yield with 0.1 mol %
catalyst loading. Even when the amount of catalyst was
increased to 0.5 mol %, 1 was still not an efficient ligand
entry 1). In sharp contrast, 3 having EG12 chains was found
Miyaura, N. In Metal-Catalyzed Cross-Coupling Reaction; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 41-123. (c)
Suzuki, A.; Brown, H. C. Organic Syntheses Via Boranes, Vol. 3, Suzuki
Coupling; Aldrich: Milwaukee, 2003.
4
4
(
6) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176–
(
4
211, and references therein. (b) Barder, T. E.; Walker, S. D.; Martinelli,
J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685–4696.
to be a much more effective ligand, affording the product in
2122
Org. Lett., Vol. 11, No. 10, 2009

9
2% yield (entry 2). To clarify the role of the EG12 chains
of 3, some control experiments were carried out with several
ligand systems. With PPh (a core part of 3), no conversion
Table 2. Reaction of Various Substrates under the Optimum
3
a
Reaction Conditions
of 4-chlorotoluene was observed (entry 3). The ligand system
consisting of a mixture of EG12-dimethyl ether (MeO-
(
CH
the product at all (entry 4). Furthermore, neither a combination
of 7 and PPh (entry 5) nor a mixture of 4 (the oxide of 3) and
PPh (entry 6) afforded the product at all. These results clearly
2 2 3
CH O)12Me, 5-Me) and PPh in place of 3 did not afford
3
3
indicate that EG12 moieties must be connected to the phosphine
core in order to cause the high efficiency as the ligand. On the
other hand, the efficiency of 3 was affected considerably by
the reaction conditions such as solvent and base. When entry 2
in Table 1 was carried out in toluene, DMF, DME, 2-propanol,
or H
tions, the yield of 4-phenyltoluene decreased to 28%, 46%, 49%,
4%, or 39%, respectively. As for a base, KF, K PO , Na CO
Cs CO , or Li CO in place of K CO in entry 4 afforded the
2
O as a solvent under otherwise identical reaction condi-
6
3
4
2
3
,
2
3
2
3
2
3
product in 83%, 90%, 49%, 45%, or 4%, respectively. Thus, 3
works as an efficient ligand in THF with the potassium bases.
These observations are very reminiscent of a catalyst system
4
using 2 as the ligand.
The effectiveness of 3 as the ligand was further confirmed
using various aryl chlorides and arylboronic acids under the
optimum reaction conditions in THF with K CO (Table 2).
2 3
The electron-rich and -poor aryl chlorides were smoothly
converted to the corresponding biphenyl compounds in high
yields (entries 1 and 2). In the more sterically demanding
coupling reaction of 2-chloro-1,3-dimethylbenzene with phe-
nylboronic acid or 2-methylphenylboronic acid, the products
were obtained in high or moderate yields (entries 3 and 4).
a
2 2
Aryl chloride (2.0 mmol), arylboronic acid (4.0 mmol), [PdCl (PhCN) ]
1
-Phenylnaphthalene was obtained either from 1-chloronaph-
thalene or chlorobenzene in high yields (entries 5 and 6).
-Fluorophenylboronic acid afforded the product in 97% yield
entry 7). From 2-chloro-thiophene and phenylboronic acid, the
desired product was obtained in 93% yield (entry 8), while
-chloropyridine was converted to the corresponding compound
(0.010 mmol, 0.50 mol %), 3 (0.020 mmol), K CO (4.0 mmol), and THF
2 3
b
(
1.0 mL) at 60 °C for 20 h. Yields of the isolated products. The data in
the parentheses show yields of the products based on the GC internal
standard technique.
4
(
2
products decreased to 47% and 50%, respectively, showing
efficacy of longer EG12 chains of 3.
in low yield, possibly as a result of the coordination of the
pyridine moiety to a catalyst center (entry 9). When 1 instead
of 3 was used as the ligand in entries 1 and 6, the yields of the
Figure 2 shows an optimized structure of 3 calculated by
10
the ONIOM (B3LYP/LANL2DZ-UFF) method, in which
(
7) For recent papers on PEG-functionalized ligands in water, see: (a)
Hong, S. H.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 3508–3509. (b)
Gallivan, J. P.; Jordan, J. P.; Grubbs, R. H. Tetrahedron Lett. 2005, 46,
2
577–2580. (c) Adidou, O.; Goux-Henry, C.; Safi, M.; Soufiaoui, M.;
Framery, E. Tetrahedron Lett. 2008, 49, 7217–7219. (d) Leyva, A.; Garc ´ı a,
H.; Corma, A. Tetrahedron 2007, 63, 7097–7111. (e) Corma, A.; Garc ´ı a,
H.; Leyva, A. J. Catal. 2006, 240, 87–99. (f) Wang, X.; Yin, L.; Yang, T.;
Wang, Y. Tetrahedron: Asymmetry 2007, 18, 108–114.
(
8) (a) Middel, O.; Verboom, W.; Reinhoudt, D. N. Eur. J. Org. Chem.
2
002, 258, 7–2597. (b) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.;
Johansson, G. J. Am. Chem. Soc. 1997, 119, 1539–1555. (c) Percec, V.;
Ahn, C.-H.; Cho, W.-D.; Jamieson, A. M.; Kim, J.; Leman, T.; Schmidt,
M.; Gerle, M.; M o¨ ller, M.; Prokhorova, S. A.; Sheiko, S. S.; Cheng, S. Z. D.;
Zhang, A.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc. 1998, 120,
8
619–8631.
(
9) (a) Allen, D. W.; Taylor, B. F. J. Chem. Soc., Dalton Trans. 1982,
5
3
1–54. (b) Socol, S. M.; Verkade, J. G. Inorg. Chem. 1984, 23, 3487–
493. (c) Andersen, N. G.; Keay, B. A. Chem. ReV. 2001, 101, 997–1030.
(
4
d) Alyea, E. C.; Malito, J. Phosphorus, Sulfur Silicon Relat. Elem. 1989,
6, 175–181.
Figure 2. Optimized structure of 3 by ONIOM (B3LYP/LANL2DZ:
UFF) method. The space-filling diagram shows the triphenylphos-
phine core.
(
10) (a) Maseras, F.; Morokuma, K. J. Comput. Chem. 1995, 16, 1170–
1
1
179. (b) Humbel, S.; Sieber, S.; Morokuma, K. J. Chem. Phys. 1996, 105,
959–1967. (c) Svensson, M.; Humbel, S.; Froese, R. D. J.; Matsubara, T.;
Sieber, S.; Morokuma, K. J. Phys. Chem. 1996, 100, 19357–19363.
Org. Lett., Vol. 11, No. 10, 2009
2123

long EG12 chains are folded around the PPh
calculation shows that the structure in Figure 2 is far more
3
core. The
Suzuki-Miyaura coupling reaction of unactivated aryl
chlorides, 3 was a highly effective ligand without the
elaborated dendritic structures such as in 2. Further applica-
tion of the unique phosphines with flexible long chains in
catalysis is currently under investigation.
stable than one with straight EG12 chains (Figure S1 in
-
1
Supporting Information) by 68 kcal mol . Thus, 3 has a
particular gigantic shape: the Connolly solvent-excluded
1
1
3
volumes of the optimized 3, 2, and PPh were 6720, 5830,
3
and 230 Å , respectively. The catalytic behavior using 3 as
the ligand was very reminiscent of one using 2 (vide supra).
The high efficiency of 2 as the ligand has been attributed
to the particular bulky structure with folded EG4 chains
Acknowledgment. This work was supported by Grant-
in-Aid for Scientific Research on Priority Areas (“Chemistry
of Concerto Catalysis” and “Synergy of Elements”) from
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan.
4
with the dendritic arrangement. In the case of 3, the same
mechanism would be operative to enhance the catalytic
activity, i.e., the phosphine of the massive shape (Figure 2)
might exclude other same phosphines (3) in the coordination
sphere to generate a highly unsaturated and hence ex-
tremely active catalyst species.
Supporting Information Available: Experimental pro-
cedures including the synthesis of 3. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
2
OL900578G
In summary, a new phosphine (3) bearing EG12 chains
was designed and synthesized. In the palladium-catalyzed
(
12) (a) Ohta, H.; Tokunaga, M.; Obora, Y.; Iwai, T.; Iwasawa, T.;
Fujihara, T.; Tsuji, Y. Org. Lett. 2007, 9, 89–92. (b) Iwasawa, T.; Komano,
T.; Tajima, A.; Tokunaga, M.; Obora, Y.; Fujihara, T.; Tsuji, Y. Organo-
metallics 2006, 25, 4665–4669.
(
11) (a) Connolly, M. L. J. Am. Chem. Soc. 1985, 107, 1118–1124. (b)
Connolly, M. L. Science 1983, 221, 709–713.
2124
Org. Lett., Vol. 11, No. 10, 2009