Pd-P(t-Bu)3-catalyzed consecutive cross-coupling of p-phenylenedizinc compound with two different electrophiles leading to unsymmetrically 1,4-disubstituted benzenes

Article abstract of DOI:10.1021/jo702103r

(Chemical Equation Presented) Pd-P(t-Bu)₃ was found to be a chemoselective catalyst for the reaction of p-phenylenedizinc compound with equimolar amounts of carbon electrophiles to afford the single cross-coupling products in good yields, effectively suppressing the formation of double cross-coupling products. The subsequent additions of other electrophiles to the resulting solutions caused the second cross-coupling of the incipient products to take place, achieving a novel and efficient one-pot synthesis of unsymmetrically 1,4-disubstituted benzenes. The origin of the observed high chemoselectivity was speculated.

Full text of DOI:10.1021/jo702103r

Pd-P(t-Bu)3-Catalyzed Consecutive
Cross-Coupling of p-Phenylenedizinc Compound
with Two Different Electrophiles Leading to
Unsymmetrically 1,4-Disubstituted Benzenes
Takahiro Kawamoto, Shogo Ejiri, Kana Kobayashi,
Shunsuke Odo, Yasushi Nishihara, and Kentaro Takagi*
Department of Chemistry, Faculty of Science, Okayama
FIGURE 1. Synthesis of p-disubstituted benzenes.
UniVersity, Tsushima, Okayama 700-8530, Japan
partners provides 1 with an unsymmetrical structure, in which
the greater the difference in reactivity between the two leaving
groups X1 and X2, the higher the degree of selectivity in the
transformation of 2 to the desired product. Thus, in such
reactions, the synthetic equivalents of 3b (possessing X1 ) I or
Br and X2 ) B, Zn, Mg, or Sn2) or 3c (possessing X1 ) I and
X2 ) Br or OTf3) have been generally employed, whereas those
of 3a have been little utilized, presumably because of the
difficulty in preparing 2 with two different kinds of elec-
trofuges.4 Hereupon, it is noted that, even if the electrofuges
are the same, i.e., X1 ) X2, the chemoselective coupling on
one site is essentially possible; the reactivity of the singly
coupled product 4 is no longer the same as that of the starting
material. Thus far, the transformations using the synthetic
equivalents of 3a have been carried out using B or Sn derivatives
along with the catalysis by Pd, thus affording unsymmetrical
terphenyls in the low yields of 13-33% by the consecutive
treatment with two kinds of aryl iodides.1f,h,n We envisaged that
the efficiency of the transformations might be improved by
making use of the more positively charged X1, causing a greater
difference between the reactivities of 2 and 4. As a metal, we
were interested in Zn (EN: B ) 2.0; Sn ) 1.8; Zn ) 1.7). We
previously reported that the reaction between iodobenzenes and
zinc powder smoothly takes place in N,N,N′,N′-tetramethylurea
(TMU) to afford the corresponding arylzinc compounds in good
takagi@cc.okayama-u.ac.jp
ReceiVed September 26, 2007
Pd-P(t-Bu)3 was found to be a chemoselectiVe catalyst for
the reaction of p-phenylenedizinc compound with equimolar
amounts of carbon electrophiles to afford the single cross-
coupling products in good yields, effectively suppressing the
formation of double cross-coupling products. The subsequent
additions of other electrophiles to the resulting solutions
caused the second cross-coupling of the incipient products
to take place, achieving a novel and efficient one-pot
synthesis of unsymmetrically 1,4-disubstituted benzenes. The
origin of the observed high chemoselectivity was speculated.
As a synthetic method of disubstituted benzenes 1, the cross-
coupling reaction between phenylene-supplying reagents 2,
synthetic equivalents of 3a-c, and their electronically matching
counterparts is useful, since the products are entirely free from
contamination by any regioisomers (Figure 1).1 In the reaction,
the consecutive treatment of 2 with two kinds of coupling
(2) X1, X2 ) B, Br: (a) Shimada, S.; Yamazaki, O.; Tanaka, T.; Rao,
M. L. N.; Suzuki, Y.; Tanaka, M. Angew. Chem., Int. Ed. 2003, 42, 1845-
1848. (b) Simoni, D.; Giannini, G.; Baraldi, P. G.; Romagnoli, R.; Roberti,
M.; Rondanin, R.; Baruchello, R.; Grisolia, G.; Rossi, M.; Mirizzi, D.;
Invidiata, F. P.; Grimaudo, S.; Tolomeo, M. Tetrahedron Lett. 2003, 44,
3005-3008. X1, X2 ) Zn, Br or I: (c) Amatore, C.; Jutand, A.; Negri, S.;
Fauvarque, J.-F. J. Organomet. Chem. 1990, 390, 389-398. (d) Krasovskiy,
A.; Malakhov, V.; Gavryushin, A.; Knochel, P. Angew. Chem., Int. Ed.
2006, 45, 6040-6044. X1, X2 ) Li, Br: (e) Banwell, M. G.; Flynn, B. L.;
Hamel, E.; Hockless, D. C. R. Chem. Commun. 1997, 207-208. X1, X2 )
Mg, Br or I: (f) Yang, X.; Rotter, T.; Piazza, C.; Knochel, P Org. Lett.
2003, 5, 1229-1231. (g) Krasovskiy, A.; Knochel, P. Angew. Chem. Int.
Ed. 2004, 43, 3333-3336. X1, X2 ) Bi, Br: (h) Rasmussen, L. K.; Begtrup,
M.; Ruhland, T. J. Org. Chem. 2006, 71, 1230-1232.
(3) See for example: X1, X2 ) I, Br or Cl: (a) Pena, M. A.; Perez, I.;
Sestelo, J. P.; Sarandeses, L. A. Chem. Commun. 2002, 2246-2247. (b)
Duan, X.-F.; Li, X.-H.; Li, F.-Y.; Huang, C.-H. Synthesis 2004, 2614-
2616. References 1p and 2b. X1, X2 ) OTf or I, Br or Cl (c) Ohe, T.;
Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58, 2201-2208. (d) Rottla¨nder,
M.; Palmer, N.; Knochel, P. Synlett 1996, 573-575. (e) Fu¨rstner, A.; Leitner,
A. Angew. Chem., Int. Ed. 2003, 42, 308-311. (f) Cho, C.-H.; Kim, I.-S.;
Park, K. Tetrahedron 2004, 60, 4589-4599. (g) Cho, C.-H.; Park, H.; Park,
M.-A.; Ryoo, T.-Y.; Lee, Y.-S.; Park, K. Eur. J. Org. Chem. 2005, 3177-
3181.
(1) See for example: X1, X2 ) Cl, Cl: (a) Mao, L. S.; Sakurai, H.;
Hirao, T. Synthesis 2004, 2535-2539. X1, X2 ) Br, Br: (b) Wu, C.-J. J.;
Xue, C.; Kuo, Y.-M.; Luo, F.-T. Tetrahedron 2005, 61, 4735-4741. (c)
Dong, C.-G.; Hu, Q.-S. J. Am. Chem. Soc. 2005, 127, 10006-10007. (d)
Uozumi, Y.; Kikuchi, M. Synlett 2005, 1775-1778. X1, X2 ) I, I: (e)
Sinclair, D. J.; Sherburn, M. S. J. Org. Chem. 2005, 70, 3730-3733. X1,
X2 ) B, B: (f) Todd, M. H.; Balasubramanian, S.; Abell, C. Tetrahedron
Lett. 1997, 38, 6781-6784. (g) Ba¨hr, A.; Felber, B.; Schneider, K.;
Diederich, F. HelV. Chim. Acta 2000, 83, 1346-1376. (h) Iovine, P. M.;
Kellett, M. A.; Redmore, N. P.; Therien, M. J. J. Am. Chem. Soc. 2000,
122, 8717-8727. (i) Chaumeil, H.; Le Drian, C.; Defoin, A. Synthesis 2002,
757-760. (j) Thiemann, T.; Umeno, K.; Wang, J.; Tabuchi, Y.; Arima, K.;
Watanabe, M.; Tanaka, Y.; Gorohmaru, H.; Mataka, S. J. Chem. Soc., Perkin
Trans. 1 2002, 2090-2110. (k) Perret-Aebi, L.-E.; von Zelewsky, A. Synlett
2002, 773-774. (l) Kalai, T.; Balog, M.; Jeko, J.; Hubbell, W. L.; Hideg,
K. Synthesis 2002, 2365-2372. (m) Mandolesi, S. D.; Vaillard, S. E.;
Podesta, J. C.; Rossi, R. A. Organometallics 2002, 21, 4886-4888. (n)
Havelkova, M.; Dvorak, D.; Hocek, M. Tetrahedron 2002, 58, 7431-7435.
X1, X2 ) Sn, Sn: (o) Siesel, D. A.; Staley, S. W. J. Org. Chem. 1993, 58,
7870-7875. (p) Bao, Z.; Chan, W. K.; Yu, L. J. Am. Chem. Soc. 1995,
117, 12426-12435. (q) Corsico, E. F.; Rossi, R. A. Synlett 2000, 230-
232. (r) Corsico, E. F.; Rossi, R. A. J. Org. Chem. 2002, 67, 3311-3316.
Reference 1m.
(4) X1, X2 ) Si, Sn: (a) Nitschke, J. R.; Zu¨rcher, S.; Tilley, T. D. J.
Am. Chem. Soc. 2000, 122, 10345-10352. X1, X2 ) Mg, B prepared
successively: (b) Christophersen, C.; Begtrup, M.; Ebdrup, S.; Petersen,
H.; Vedso, P. J. Org. Chem. 2003, 68, 9513-9516. X1, X2 ) Mn, Mn
prepared successively: (c) Rieke, R. D.; Kim, S.-H.; Wu, X. J. Org. Chem.
1997, 62, 6921-6927. X1, X2 ) Mg, Mg prepared successively: ref 2f.
10.1021/jo702103r CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/17/2008
J. Org. Chem. 2008, 73, 1601-1604
1601

TABLE 1. Effect of Ligand on Pd-Catalyzed Reaction of 5 or 14a
SCHEME 1. Synthesis of Symmetrically 1,4-Disubstituted
Benzenes
yieldb/%
property of L
entry
L
12 15
9
17
øc
θd/deg
yields.5 In this paper, we intended to achieve the efficient
synthesis of 1 with unsymmetrical structures starting from the
synthetic equivalent of 3a using the readily available Zn
derivatives of 2, X1 ) X2 ) ZnI, through the investigation
into the effect of the phosphorus ligand affecting the discrimi-
nating ability of the Pd catalyst between the reactivities of 2
and 4.
First, to see the utility of the zinc compound, 1,4-bis-
(iodozinc)benzene 5, in the Negishi reaction, the cross-coupling
with various aryl iodides 6a-c or aroyl chlorides 7a (2.4 equiv)
was carried out in the presence of Pd(PPh3)4.6 The obtained
results, summarized in Scheme 1, show that the desired products
8-11, symmetrically 1,4-disubstututed benzenes, were obtained
in good yields under mild conditions, proving that the compound
is superior to the corresponding B1g-n or Sn derivatives1n-r in
the related Pd-catalyzed reactions, with respect to the employed
conditions and/or yields.1h,i,n-p
The reaction of 5 with 4-iodo(trifluoromethyl)benzene 6b (1.0
equiv) was examined to determine if the single cross-coupling
product was selectively obtained upon decreasing the amount
of carbon electrophiles to one-half of the amount used in Scheme
1. After the stirring of the solution for 1 h at room temperature,
the resulting solution, treated with I2 to determine the yield of
4′-(trifluoromethyl)biphenyl-4-ylzinc iodide 12 as its derivative,
4-iodo-4′-(trifluoromethyl)biphenyl 13, showed the presence of
12 in 69% yield along with 10% of the double coupling product
9 (entry 1 in Table 1). Although the yield of 12 might be
satisfactory for practical use, a higher one is desirable, due to
the difficulty in purifying the arylzinc compounds.
The effect of the ligands was then investigated using the
palladium catalysts, generated in situ from PdCl2(C6H5CN)2 and
various phosphorus ligands possessing individual electronic and
sterically demanding properties. The obtained results are sum-
marized in Table 1 together with the electronic parameter ø7
and steric parameter θ8 of the ligands.
1e
2
3
4
5
6
7
8
9
10
11
12f
13g
14h
15
16
17
18
Ph3P
P1
69
64
60
66
70
72
49
59
63
54
10
13
12
10
9
13.25
10.5
11.5
13.25
16.8
20.5
-8
10.65
34.8
5.25
0
145
145
145
145
145
145
184
178
184
136
182
(p-CH3OC6H4)3P P2
(p-CH3C6H4)3P
Ph3P
(p-ClC6H4)3P
(p-CF3C6H4)3P
TTMOP
(o-CH3C6H4)3P
(C6F5)3P
Bu3P
t-Bu3P
t-Bu3P
t-Bu3P
t-Bu3P
(p-CH3C6H4)3P
Ph3P
(p-CF3C6H4)3P
t-Bu3P
P3
P4
P5
P6
P7
P8
P9
8
15
14
11
14
7
5
6
8
P10 78
78
80
80
46
49
59
73
18
15
14
8
11.5
13.25
20.5
0
145
145
145
182
a 5 or 14 (0.5 mmol), 6b (0.5 mmol), PdCl2(PhCN)2 (0.005 mmol), L(0.02
mmol), TMU (0.3 mL), and THF (2.5 mL) were used in every run. b GLC
yield. Yield of 12 or 15 was calculated from 4- or 3-iodo-4′-trifluorom-
ethylbiphenyl 13 or 16, respectively, obtained by the I2 treatment of the
reaction solutions. c ø ) electronic parameter. d θ ) steric parameter, cone
angle. e Pd(PPh3)4 was used in place of PdCl2(PhCN)2. f Bis(dibenzylide-
neacetone)palladium was used in place of PdCl2(PhCN)2. g Bis[(η3-allyl)-
µ-chloropalladium] (0.0025 mmol) was used in place of PdCl2(PhCN)2.
h Bis[(η3-allyl)-µ-chloropalladium] (0.000025 mmol) and P(t-Bu)3 (0.0002
mmol) were used.
As for a series of triarylphosphines with θ ) 145°, the yield
of 12 seemingly became higher along with the concomitant
decreases in the yield of 9, when the electron-donating property
was low (entries 1-6). Eventually, based on the utility of tris-
{4-(trifluoromethyl)phenyl}phosphine, a 72% yield of 12 and
the selectivity between 12 and 9 of 9.0 were attained. As
expected, the steric bulkiness of the ligand did not necessarily
increase the yield of 12 (entries 7-9), in contrast to its beneficial
effect in our previous study with the o-phenylenedizinc com-
pound, in which the Pd catalyst containing the bulky tris(2-
methylphenyl)phosphine or tris(2,4,6-trimethoxyphenyl)phos-
phine (TTMOP) afforded the highest selectivity between the
single/double coupling products.9 Among the examined trialky-
lphosphines, P(Bu)3, θ ) 136°, gave a rather poorer result than
the ordinary triarylphosphines (entry 10), presumably due to
the stronger electron-donating ability, whereas P(t-Bu)3 attained
the highest yield of 12, 78%, and the selectivity between 12
and 9 of 11.1 (entry 11). It is noted that P(t-Bu)3 belongs to the
phosphines that are not only the most electron-donating but also
the most bulky (Scheme 2). Therefore, the observed selectivity
exerted by Pd-P(t-Bu)3 is of interest. An equally effective
catalyst was also available from P(t-Bu)3 and other precursors
such as bis(dibenzylideneacetone)palladium or bis[(η3-allyl)-
µ-chloropalladium] (entries 12 and 13), and the amount of the
(5) (a) Takagi, K. Chem. Lett. 1993, 469-472. (b) Takagi, K.; Shimoishi,
Y.; Sasaki, K. Chem. Lett. 1994, 2055-2088. (c) Okano, M.; Amano, M.;
Takagi, K. Tetrahedron Lett. 1998, 39, 3001-3004. (d) Ogawa, Y.; Saiga,
A.; Mori, M.; Shibata, T.; Takagi, K. J. Org. Chem. 2000, 65, 1031-1036.
(e) Ikegami, R.; Koresawa, A.; Shibata, T.; Takagi, K. J. Org. Chem. 2003,
68, 2195-2199.
(6) To the best of our knowledge, the direct synthesis of p- or
m-phenylenedizinc compound 5 or 14 from the corresponding dihalobenzene
and zinc powder has not been reported. For the direct synthesis of 5 using
activated zinc, see: (a) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J. Org.
Chem. 1991, 56, 1445-1453. For the direct synthesis of 5 or 14 using zinc
powder in the presence of Co catalyst, see: (b) Kazmierski, I.; Gosmini,
C.; Paris, J.-M.; Perichon, J. Tetrahedron Lett. 2003, 44, 6417-6420. (c)
Fillon, H.; Gosmini, C.; Perichon, J. J. Am. Chem. Soc. 2003, 125, 3867-
3870. (d) Fillon, H.; Gosmini, C.; Nedelec, J.-Y.; Perichon, J. Tetrahedron
Lett. 2001, 42, 3843-3846. For the application of 5 to the Negishi reaction,
the synthesis of polymer from 5 was only reported: (e) Mellah, M.; Labbe,
E.; Nedelec, J.-Y.; Perichon, J. New J. Chem. 2002, 26, 207-212.
(7) (a) Bartik, T.; Himmler, T.; Schulte, H. G.; Seevogel, K. J.
Organomet. Chem. 1984, 272, 29-41. (b) Liu, H. Y.; Eriks, K.; Prock, A.;
Giering, W. P. Organometallics 1990, 9, 1758-1766.
(8) Tolman, C. A. Chem. ReV. 1977, 77, 313-348.
(9) Saiga, A.; Hossain, K. M.; Takagi, K. Tetrahedron Lett. 2000, 41,
4629-4632.
1602 J. Org. Chem., Vol. 73, No. 4, 2008

TABLE 2. Pt-P(t-Bu)3-Catalyzed Consecutive Reaction of 5 with Two Different Electrophilesa
yieldb
(%)
entry
R1-X
Y-X
product
1
2
3
4
5
6
7
8
9
p-CF3C6H4-I
C6H5CO-Cl
C6H5-I
6b
7b
6d
6e
6b
6b
6e
6g
6g
6i
I-I
I-I
I-I
I-I
13
18
19
20
21
22
23
24
25
26
27
28
(78)
(81)
(70)
(68)
76
78
56
61
55
p-C2H5C6H4-I
p-CF3C6H4-I
p-CF3C6H4-I
p-C2H5C6H4-I
o-C2H5C6H4-I
o-C2H5C6H4-I
p-NO2C6H4-I
p-CF3C6H4-I
p-CF3C6H4-I
p-CH3OC6H4-I
p-C2H5O2CC6H4-I
p-CH3COC6H4-I
p-CH3COC6H4-I
o-CH3COC6H4-I
C6H5CH2-Br
6c
6a
6f
6f
6h
6j
10
11
12
59
68
78
6b
6b
(Z)-CH3O2CCHdCH-I
C6H5CO-Cl
6k
7b
a Molar ratio: 5/R-X/Y-X/Pd-t-Bu3P ) 1:1:1.2:0.01. In entries 1-4, I2 was used in excess. b Isolated yield. Yields in parentheses determined by GLC.
SCHEME 2. Relationship between Log{(yield of 12)/(yield
of 9)} and σ-Donicity of Ligand, ø
P(t-Bu)3 retained the catalytic activity. Thus, the subsequent
additions of other carbon electrophiles such as 6a, 6c, 6f, 6h,
6j, 6k, or 7b (1.2 equiv) to the resulting solutions readily caused
their catalytic cross-coupling with the incipient products to take
place. The results summarized in Table 2 show that a wide
variety of unsymmetrically 1,4-disubstituted benzenes, contain-
ing 4-CF3-, 4-NO2-, 4-C2H5-, or 2-C2H5-substituted phenyl group
as the first introduced substituent and 4-C2H5OCO-, 4-CH3CO-,
4-CH3O-, or 2-CH3CO-substituted phenyl, alkenyl, benzyl, or
aroyl groups as the second introduced substituent, was obtained
in good yield (entries 5-12). Thus, based on the utility of 5
and the specific catalysis by Pd-P(t-Bu)3, the novel and efficient
one-pot synthesis of unsymmetrically1,4-disubstituted benzenes
from the p-phenylenedimetallic compound was achieved.
Finally, it might be worthy to consider the reason for the
high chemoslectivity achieved by Pd-P(t-Bu)3, because the
results are concerned with the transmetallation reaction involved
in the catalytic cycle (vide infra), of which there is limited
mechanistic information.10 In Scheme 3, prepared by application
of the general catalytic cycle of the Negishi reaction to the
present one, the double coupling product C, like 9, is formed
from the single coupling product B, like 12, through cycle II,
wherein exists a competition for the oxidative adduct A between
B and 5, the latter of which belongs to cycle I yielding B. During
the competitive transmetallation, among the various examined
Pd-L (Table 1), Pd-P(t-Bu)3 significantly discriminated the
difference in the reactivity between 5 and B, resulting in
producing B with the highest yield.11 Each of the ligands L
conferred an individual catalytic efficiency on A, depending
on its electronic property and/or steric bulkiness; however, P(t-
Bu)3 seems to deviate from the standard effect. That is, as shown
catalyst was reduced to 0.01 mol % without any significant drop
in the efficiency in the catalysis (entry 14).
To see if the efficiency of Pd-P(t-Bu)3 is ubiquitously
observed in phenylene systems, the reactions of the m-
phenylenedizinc compound 146 with 6b were examined. The
results show that, in comparison with a series of Pd-tri-
arylphosphines, Pd-P(t-Bu)3 exhibited a far more effective
catalysis, affording a 73% yield of the desired product, 4′-
(trifluoromethyl)biphenyl-3-ylzinc iodide 15, detected as 3-iodo-
4′-(trifluoromethyl)bipenyl 16 via I2 treatment, and the selec-
tivity between 15 and the double coupling product, 4,4′′-
bis(trifluoromethyl)-1,1′:3′,1′′-terphenyl 17, of 9.1 (entries 15-
18). Interestingly, with respect to each ligand, the yield of a
single coupling product and the selectivity were lower than the
respective ones with 5 (entries 3, 4, 6, and 11).
Encouraged by the established validity of Pd-P(t-Bu)3 in the
reaction between 5 and 6b, the utility of other electrophiles 6d,
6e, 7b in the catalytic reaction was examined. The obtained
results, summarized in Table 2, show that, similar to 6b, the
aroyl chloride was subject to the efficient catalysis by Pd-P(t-
Bu)3, yielding the desired product 18, derived from the single
coupling product through the second reaction with I2, in a high
yield (entry 2), and iodobenzenes, even without an electron-
withdrawing substituent, also afforded the desired products 19,
20 in good yields (entries 3, 4).
(10) For a general catalytic cycle of Pd-catalyzed cross-coupling including
the Negishi reaction, see for example: (a) Tamao, K.; Miyaura, N. In Cross-
Coupling Reactions; Miyaura, N., Ed.; Springler: Berlin, 2002; pp 4-7.
For a transmetallation of arylpalladium complexes, see for example: (b)
Suzaki, Y.; Yagyu, T.; Osakada, K. J. Organomet. Chem. 2007, 692, 326-
342. (c) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
4704-4734. (d) Casares, J. A.; Espinet, P.; Fuentes, B.; Salas, G. J. Am.
Chem. Soc. 2007, 129, 3508-3509.
(11) (a) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okukado,
N. J. Am. Chem. Soc. 1987, 109, 2393-2401. (b) Amatore, C.; Jutand, A.
In Handbook of Organopalladium Chemistry; Negishi, E., Ed.; John Wiley
& Sons: New York 2002; pp 943-965. See the Supporting Information
(SI) for the details.
Fortunately, after the reactions of 5 with an equimolar amount
of electrophiles such as 6b, 6e, 6g, or 6i were completed, Pd-
J. Org. Chem, Vol. 73, No. 4, 2008 1603

SCHEME 3. Catalytic Cycle
SCHEME 4. Discrimination of Reactivity between 5 and B
an equimolar amount of aryl or aroyl electrophiles to afford
the single coupling products in high yields,17 which allowed
the novel and efficient access to unsymmetrically 1,4-disubsti-
tuted benzenes through the one-pot procedure.
Experimental Section
General Procedure for the Palladium-Catalyzed Consecutive
Cross-Couplng of Phenylenedizinc Compound 5 with Two
Kinds of Carbon Electrophiles. Preparation of 4-Methoxy-4′′-
trifluoromethyl-1,1′:4′,1′′-terphenyl 21. To PdCl2(PhCN)2 (1.9
mg, 0.005 mmol) was added THF (0.1 mL) and 0.059 mL of a
hexane solution of P(t-Bu)3 (0.020 mmol), then the mixture was
stirred for 5 min at room temperature. To the mixture was next
added a 2.8 mL of THF/TMU solution of 5 (0.50 mmol) and
4-iodobenzotrifluoride 6b (0.090 mL, 0.50 mmol); the mixture was
stirred for 1 h at room temperature. To the resulting mixture,
p-iodoanisole 6c (131 mg, 0.60 mmol) was added and stirred for 3
h at room temperature. After the treatment of the resulting mixture
with aqueous HCl, the CHCl3 extract was thin layer chromato-
graphed on silica gel affording 125 mg of 21 (76%): mp 196-
in Scheme 2, for both G1 θ e 145° and G2 θ > 145°, forming
A of ArPdXL2 and of ArPdXL, respectively,12 the selectivity
tended to increase as the electron-donating ability of L
decreased, although the degrees of the increase in G1 and of G2
were not the same, with the exception of P(t-Bu)3. As the special
effect by P(t-Bu)3, the agostic interaction in ArPdI(P(t-Bu)3)
brings about the noted strengthening of the bond between Pd
and I.13,14 Such a strong Pd-I probably made the replacement
of I with the weaker nucleophile B much more difficult, which
might be the origin of the high chemoselectivity15 (Scheme 4).
As for G1 or G2, A containing the weakly electron-donating L
should possess a strong corresponding bond, obeying the trans
influence rule. This fact might support the hypothesis.
1
197 °C; IR (KBr) 1259 cm-1, 1336 cm-1; H NMR (300 MHz,
In conclusion, Pd-P(t-Bu)3 catalyst achieved the chemose-
lectiVe cross-couplings of p-phenylenedizinc compounds with
CDCl3) δ 3.87 (s, 3H), 7.01 (d, J ) 8.8 Hz, 2H), 7.59 (d, J ) 8.9
Hz, 2H), 7.67-7.73 (m, 8H); 13C NMR (126 MHz, CDCl3/C2H2-
Cl4) δ 55.3, 114.3, 124.2 (q, J ) 272.1 Hz), 125.6 (q, J ) 3.9 Hz),
127.1, 127.5, 128.0, 129.1 (q, J ) 32.5 Hz), 132.7, 137.8, 140.5,
144.1, 159.3; Anal. Calcd for C20H15F3O: C, 73.16; H, 4.60.
Found: C, 73.10; H, 5.00.
(12) (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030-
3039. (b) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598-
11599. (c) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9550-9561. (d) Littke, A. F.; Dai, C.; Fu, G. C. J.
Am. Chem. Soc. 2000, 122, 4020-4028. (e) Casares, J. A.; Espinet, P.;
Salas, G. Chem. Eur. J. 2002, 8, 4843-4853.
(13) Stambuli, J. P.; Bu¨hl, M.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 9346-9347.
(14) The bond distance between Pd and I in the complex, 2.613A, is
one of the shortest among the various ArPdI complexes containing the
phosphorus ligand. See the SI, for the details.
Supporting Information Available: General method, relation-
ship between log([B]/[C]) and log k/k′, the bond distance between
Pd and I in ArPdI complexes, compound characterization data. This
material is available free of charge via Internet at http://pubs.acs.org.
JO702103R
(15) We measured the 19F NMR of p-fluorophenylzinc compound to
determine the field/inductive parameter cσ of p-ZnI group.16 The observed
cσ constant for p-ZnI, -0.32, was smaller than the values reported for
p-C6H5, 0.01, and p-C6H5CO, 0.41, which means that 5 possesses a stronger
nucleophilicity than the single coupling product B. A similar run with the
m derivative showed that m-ZnI, cσ constant -0.29, also possesses a stronger
electron-donating ability than m-C6H5, 0.06, or m-C6H5CO, 0.32.
(16) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165-195.
(17) Pd-P(t-Bu)3 affords the double coupling products selectively in the
reaction of dihalobenzenes with equimolar amounts of arylboronic acids:
Reference 1e. See also: Yokoyama, A.; Suzuki, H.; Kubota, Y.; Ohuchi,
K.; Higashimura, H.; Yokozawa, T. J. Am. Chem. Soc. 2007, 129, 7236-
7237.
1604 J. Org. Chem., Vol. 73, No. 4, 2008