A bowl-shaped phosphine as a ligand in palladium-catalyzed Suzuki-Miyaura coupling of aryl chlorides: Effect of the depth of the bowl

Article abstract of DOI:10.1021/ol0626138

(Chemical Equation Presented) Bowl-shaped phosphine ligands were found to be highly effective in Suzuki-Miyaura coupling of unactivated aryl chlorides, in which the depth of the bowl affected the catalytic activity considerably.

Full text of DOI:10.1021/ol0626138

ORGANIC
LETTERS
2007
Vol. 9, No. 1
89-92
A Bowl-Shaped Phosphine as a Ligand
in Palladium-Catalyzed Suzuki Miyaura
−
Coupling of Aryl Chlorides: Effect of
the Depth of the Bowl
Hidetoshi Ohta,†,‡ Makoto Tokunaga,‡ Yasushi Obora,‡ Tomohiro Iwai,‡
Tetsuo Iwasawa,‡ Tetsuaki Fujihara,† and Yasushi Tsuji*,†
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto UniVersity, CREST, Japan Science and Technology Agency (JST),
Kyoto 615-8510, Japan, and Catalysis Research Center and DiVision of Chemistry,
Graduate School of Science, Hokkaido UniVersity, Sapporo 001-0021, Japan
ytsuji@scl.kyoto-u.ac.jp
Received October 24, 2006
ABSTRACT
Bowl-shaped phosphine ligands were found to be highly effective in Suzuki−Miyaura coupling of unactivated aryl chlorides, in which the
depth of the bowl affected the catalytic activity considerably.
Phosphines are one of the most important ligands in a
homogeneous transition-metal-catalyzed reaction. Therefore,
a wide variety of phosphines have been designed to realize
high catalytic activity and selectivity.1 Recently, a bowl-
shaped phosphine (BSP) has attracted much attention,2
because BSP has a very unique shape.3 Goto and Kawashima
reported the first example of BSP, tris(2,2′′,6,6′′-tetramethyl-
m-terphenyl-5′-yl)phosphine (2; Figure 1).2a,b Figure 2 shows
optimized structures of 2 as a representative BSP and P(t-
Bu)3 by HF/6-31G(d) calculations,4a using initial structures
optimized by CONFLEX4b/MM34c,d (HF/6-31G(d)-CON-
FLEX/MM3). As shown in Figure 2, both 2 and P(t-Bu)3
are obviously very bulky. However, the nature of the
bulkiness is quite different between these two phosphines.
The bulkiness of 2 occurs on the periphery of the phosphine
(at the rim of the bowl) with substantial empty space around
the phosphorus atom. In contrast, P(t-Bu)3 has severe steric
congestion within close proximity of the phosphorus atom.
We recently reported the first application of BSP as a ligand
in a transition-metal-catalyzed reaction, and found remarkable
rate enhancement by BSP in the rhodium-catalyzed hydrosi-
(2) (a) Goto, K.; Ohzu, Y.; Sato, H.; Kawashima, T. 15th International
Conference on Phosphorus Chemistry, Sendai, Japan, 2001; Abstr. No.
PB072. (b) Goto, K.; Ohzu, Y.; Sato, H.; Kawashima, T. Phosphorus, Sulfur,
Silicon Relat. Elem. 2002, 177, 2179. (c) Matsumoto, T.; Kasai, T.; Tatsumi,
K. Chem. Lett. 2002, 346-347. (d) Niyomura, O.; Tokunaga, M.; Obora,
Y.; Iwasawa, T.; Tsuji, Y. Angew. Chem., Int. Ed. 2003, 42, 1287-1289.
(e) Ohzu, Y.; Goto, K.; Kawashima, T. Angew. Chem., Int. Ed. 2003, 42,
5714-5717. (f) Niyomura, O.; Iwasawa, T.; Sawada, N.; Tokunaga, M.;
Obora, Y.; Tsuji, Y. Organometallics 2005, 24, 3468-3475. (g) Ohzu, Y.;
Goto, K.; Sato, H.; Kawashima, T. J. Organomet. Chem. 2005, 690, 4175-
4183.
† Kyoto University.
‡ Hokkaido University.
(1) (a) Homogeneous Catalysis with Metal Phosphine Complexes;
Pignolet, L. H., Ed.; Plenum: New York, 1983. (b) Brandsma, L.;
Vasilevsky, S. F.; Verkruijsse, H. D. Applications of Transition Metal
Catalysts in Organic Synthesis; Springer: Berlin, Germany, 1999. (c)
Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and
Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, CA, 1987; pp 523-919.
10.1021/ol0626138 CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/07/2006

Figure 2. Optimized structures of (a) 2 and (b) P(t-Bu)3 by HF/
6-31G(d)-CONFLEX/MM3.
Recently, Fu and Buchwald have shown that catalyst
systems with very basic and bulky phosphines are effective
in Suzuki-Miyaura coupling of unactivated aryl chlorides.7
Such bulky phosphines are also effective ligands in the
Mizoroki-Heck reaction of unactivated aryl chlorides.8
Actually, P(t-Bu)3 and tricyclohexylphosphine (PCy3) ef-
fectively worked as ligands in the coupling of 4-chlorotoluene
with phenylboronic acid in the presence of Pd(dba)2 with
Cs2CO3 as a base in dioxane at 80 °C7a as shown in Scheme
1. To evaluate the effectiveness of the BSP ligand in Suzuki-
Figure 1. Bowl-shaped phosphines.
lylation of ketone.2d,f During our continuous effort to explore
the efficacy of BSP as a ligand in transition-metal-catalyzed
reactions, we found a new efficiency of BSP and wish to
report that BSP is a highly effective ligand in the palladium-
catalyzed Suzuki-Miyaura coupling of unactivated aryl
chlorides.
The palladium-catalyzed Suzuki-Miyaura coupling is one
of the most important and versatile methods for construction
of carbon-carbon bonds.5 It is well-known that Suzuki-
Miyaura coupling is considerably affected by the nature of
the catalyst precursor, the added base, and solvent.5 There-
fore, the proper choice of reaction conditions is very impor-
tant to evaluate the effect of a ligand in Suzuki-Miyaura
coupling. In the present study, five BSP ligands (1-5 in
Figure 1) were employed. They are phosphines having
m-terphenyl (1-4) or the higher dendritic moieties (56).
Scheme 1
Miyaura coupling, we carried out the reaction with BSP
ligands under the same reaction conditions. The BSP ligand
1 having a m-terphenyl moiety without any substituents
afforded the product only in 2% yield. On the other hand,
the BSP ligands 2 and 4 bearing methyl substituents at the
2,2′′,6,6′′ positions of the m-terphenyl moiety and the BSP
ligand 5 bearing the higher dendritic moiety afforded the
product in much higher yields (75-91%). Thus, the BSPs
with the methyl substituents were found to be effective
ligands that are comparable to the very basic and bulky
phosphine (Scheme 1).
(3) For utilization of bowl-shaped molecules and moieties, see: (a)
Maverick, E.; Cram, D. J. ComprehensiVe Supramolecular Chemistry;
Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Eds.;
Elsevier: Oxford, UK, 1996; Vol. 2, pp 367-418. (b) Goto, K.; Okumura,
T.; Kawashima, T. Chem. Lett. 2001, 1258-1259. (c) Goto, K.; Nagahama,
M.; Mizushima, T.; Shimada, K.; Kawashima, T.; Okazaki, R. Org. Lett.
2001, 3, 3569-3572. (d) Naiki, M.; Shirakawa, S.; Kon-i, K.; Kondo, Y.;
Maruoka, K. Tetrahedron Lett. 2001, 42, 5467-5471.
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Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin,
K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
Revision C.02; Gaussian, Inc.: Wallingford CT, 2004. (b) Goto, H.; Osawa,
E. J. Am. Chem. Soc. 1989, 111, 8950-8951. Goto, H.; Osawa, E. J. Chem.
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519.
The BSPs are still effective even at a lower reaction
temperature (50 °C) with KF as a base in THF7b (eq 1, Table
1). Although the BSP ligand 1 afforded the product only in
1% yield (entry 1), the BSP ligands 2, 3, 4, and 5 afforded
(6) The phosphine 5 and palladium(II) complexes bearing 5 were first
reported by Goto and Kawashima: Ohzu, Y.; Goto, K.; Sato, H.;
Kawashima, T. presented in part at The 49th Symposium on Organometallic
Chemistry, Japan, 2002; Abstr. No. PA110.
(7) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387-
3388. (b) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020-4028. (c) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald,
S. L. J. Am. Chem. Soc. 2005, 127, 4685-4696. (d) Littke, A. F.; Fu, G.
C. Angew. Chem., Int. Ed. 2002, 41, 4176-4211 and references cited therein.
(e) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan,
S. P. J. Am. Chem. Soc. 2006, 128, 4101-4111.
(5) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (b)
Miyaura, N. Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A.,
Diederich, F., Eds.; Willy-VCH: Weinheim, Germany, 2004; Vol. 1, pp
41-123.
(8) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989-
7000. (b) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10-11.
90
Org. Lett., Vol. 9, No. 1, 2007

determined. Thus, neither the basicity nor the cone angle
showed evident correlations with the efficacy of the phos-
phines. Hence, we turned our attention to the shape of BSP.
The depths (d) and the diameters (l) of BSP (1-5) were
measured on the optimized structures obtained by the HF/
6-31G(d)-CONFLEX/MM3 calculations, and listed in Table
2. We previously reported that the depth of the bowl (d),
Table 1. Effect of Phosphine Ligands on the Suzuki-Miyaura
Coupling of 4-Chlorotoluene with Phenylboronic Acida
basicity
cone angle
(deg)b
yield
(%)d
Table 2. Depths and Diameters of BSPsa
b
entry
ligand
Vmin
1JP-Se
1
2
3
4
5
6
7
8
9
1
2
3
4
-41.6
-41.0
-42.8
-42.5
-39.8
-42.2
-44.4
-44.6
-54.4
-54.4
766
770
741
743
770
735
732
-
686
674
193
205
210
221
268
168
218
243
181
188
1
50
74
86
89 (88e)
0
1
5
PPh3
P(o-tol)3
P(Mes)3
P(t-Bu)3
PCy3
phosphine
d [nm]
l [nm]
c
0
0 (5f)
13 (46f)
1
2
3
4
5
0.132
0.208
0.280
0.391
0.674
1.95
1.99
2.16
2.40
2.63
10
a Reaction conditions: 4-chlorotoluene (1.0 mmol), phenylboronic acid
(1.5 mmol), KF (3.0 mmol), THF (1 mL), Pd2(dba)3‚CHCl3 (0.005 mmol),
ligand (0.010 mmol), P/Pd ) 1, 50 °C, 15 h. b HF/6-31G(d). c Corresponding
phosphine selenide is not available. d GC yield. e Isolated yield. f Reaction
under reflux.
a By HF/6-31G(d), using initial structures optimized by CONFLEX/
MM3.
the product in 50%, 74%, 86%, and 89% yields, respectively
(entries 2-5). In contrast, representative triarylphosphines
such as PPh3, P(o-tol)3, and P(Mes)3 gave almost no coupling
adduct (entries 6-8). P(t-Bu)3 and PCy3 were not so effective
as shown in entries 9 and 10.
not the diameter (l), is a critical parameter to determine the
effectiveness of the BSP ligands in the rhodium-catalyzed
hydrosilylation of ketones.2d,f In Table 1, the deeper bowls
(2-5) are apparently effective, but the shallower bowl (1)
is not, which is very reminiscent of the rhodium-catalyzed
hydrosilylation of ketones with BSP.2d,f
As shown in Scheme 1 and Table 1, the BSP ligands 2-5
are effective in Suzuki-Miyaura coupling of 4-chlorotoluene.
However, the structurally comparable 1 is not effective. To
elucidate the unusual effectiveness of BSP in the coupling
reaction, two critical parameters, basicity and cone angle,
of the phosphines were examined. So far, these two electronic
and steric parameters successfully rationalized the influence
of phosphine ligands in many transition-metal-catalyzed
reactions.1 The basicity of phosphines was evaluated by two
methods: theoretical calculation (HF/6-31G(d)) of the mo-
lecular electrostatic potential (Vmin;9 more negative values
The effect of the depth of the bowl on the catalytic activity
was further examined with various aryl chlorides by using
BSP/Pd2(dba)3‚CHCl3 catalyst in THF (Table 3). In the
reaction of 2-chloro-1,3-dimethylbenzene with phenylboronic
acid, the product was obtained in 91%, 91%, 40%, and 68%
yields with BSPs 5, 4, 3, and 2, respectively (entries 1-4).
In the more sterically demanding coupling reaction of
2-chloro-1,3-dimethylbenzene with 2-methylphenylboronic
acid employing K3PO4 as a base, the deepest BSP 5 provided
the product in much higher yield (89%) than with BSP 4, 3,
and 2 (57%, 36%, and 36% yields, respectively) (entries
6-9). Among BSPs, the deepest BSP 5 is also the most
effective ligand with the activated aryl chloride by the
electron-withdrawing substituent (entries 11-15). Although
the reactions of 4-chloroanisole were sluggish, the highest
yield was obtained with 5 (entry 16). With 2-chloropyridine
as a heteroaryl chloride, the deepest BSP 5 still was the most
effective ligand (entry 21). In this case, however, some
deeper BSPs (4 and 3: entries 22 and 23) were far less
efficacious, and the shallower ligand (1) afforded the product
in high yield (entry 25). Coordination of the pyridine
functionality to a catalyst center12 may affect the influence
of the depth of BSP.
1
indicate more basic phosphines) and JP-Se coupling con-
stants10 of the corresponding phosphine selenides SedPR3
(smaller values correspond to higher basicity). In addition,
the cone angles of the phosphines were measured according
to Tolman’s definition11 by using structures optimized by
the HF/6-31G(d)-CONFLEX/MM3 calculations. These elec-
tronic and steric parameters are listed in Table 1. As shown
in Table 1, the effective (2-5) and the ineffective (1) BSP
have essentially similar basicity comparable to that of
triarylphosphines such as PPh3. Furthermore, a particular
range of the cone angles for the effective ligands cannot be
(9) Suresh, C. H.; Koga, N. Inorg. Chem. 2002, 41, 1573-1578.
(10) (a) Allen, D. W.; Taylor, B. F. J. Chem. Soc., Dalton Trans. 1982,
51-54. (b) Socol, S. M.; Verkade, J. G. Inorg. Chem. 1984, 23, 3487-
3493. (c) Andersen, N. G.; Keay, B. A. Chem. ReV. 2001, 101, 997-1030.
(d) Alyea, E. C.; Malito, J. Phosphorus, Sulfur, Silicon Relat. Elem. 1989,
46, 175-181.
(12) (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030-
3039. (b) Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1996, 61, 7240-
7241.
(11) Tolman, C. A. Chem. ReV. 1977, 77, 313-348.
Org. Lett., Vol. 9, No. 1, 2007
91

Table 3. Suzuki-Miyaura Coupling of Various Aryl
Chloridesa
Figure 3. Effect of P/Pd on the Suzuki-Miyaura coupling of
4-chlorotoluene with phenylboronic acid (eq 1). Yields were 50%,
88%, and 1% with 2; 74%, 7%, and 2% with 3; 86%, 12%, and
2% with 4; and 89%, 43%, and 2% with 5, at P/Pd ) 1, 2, and 3,
respectively.
conditions, might be predominant. It is well-known that
bowl-shaped molecules stabilize highly reactive species
within the bowl very effectively.13 In the catalytic reaction,
deeper BSP ligands could generate highly unsaturated
monophosphine Pd species efficiently, since the deeper bowl
ligand would exclude the other identical deeper ligand on
coordination. The highly unsaturated monophosphine Pd
species thus obtained have deeper bowl-shaped cavities
(empty space) around a metal center and are expected to
have very high catalytic activity.
In summary, BSP ligands were found to be highly effective
in the palladium-catalyzed Suzuki-Miyaura coupling of
unactivated aryl chlorides. The depth of the bowl affected
the catalytic activity considerably: the deeper bowl ligand
was more effective than the shallower bowls. Further
catalytic application of BSP as a ligand is currently being
investigated.
a Reaction conditions: aryl chloride (1.0 mmol), arylboronic acid (1.5
mmol), base (3.0 mmol), THF (1 mL), Pd2(dba)3‚CHCl3 (0.005 mmol),
ligand (0.010 mmol), P/Pd ) 1. b Arylboronic acid (2.0 mmol). c GC yield,
isolated yield in parentheses.
It is noteworthy that with effective BSPs 2-5 as the ligand
the P/Pd ratio affects the catalytic activity significantly
(Figure 3). At P/Pd ) 1, BSPs 2, 3, 4, and 5 afforded the
product in 50%, 74%, 86%, and 89% yields in eq 1,
respectively (entries 2-5 in Table 1 and Figure 3). However,
at P/Pd ) 2, the yield with 3, 4, and 5 decreased dramatically
to 7%, 12%, and 43%, respectively (Figure 3). At P/Pd ) 3,
all the yields with 3, 4, and 5 further decreased to 2% (Figure
3). On the other hand, with 2 the yield of the product
considerably increased to 77% at P/Pd ) 1.2 (not shown in
Figure 3), and to 88% at P/Pd ) 2, but decreased drastically
to 1% at P/Pd ) 3 (Figure 3). In the presence of an excess
of phosphines, bis- and trisphosphine Pd species, which have
almost no catalytic activity under the present reaction
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL0626138
(13) (a) Goto, K.; Tokitoh, N.; Okazaki, R. Angew. Chem., Int. Ed. Engl.
1995, 34, 1124-1126. (b) Shimada, K.; Goto, K.; Kawashima, T.; Takagi,
N.; Choe, Y.; Nagase, S. J. Am. Chem. Soc. 2004, 126, 13238-13239.
92
Org. Lett., Vol. 9, No. 1, 2007