A highly effective and practical biaryl synthesis with triallyl(aryl) silanes and aryl chlorides

Article abstract of DOI:10.1246/cl.2004.632

A general and convenient approach for the palladium-catalyzed cross-coupling of triallyl(aryl)silanes, stable and easily accessible arylsilanes, with aryl chlorides has been demonstrated. The scope of the reaction is broad and a wide variety of functional groups are tolerant to the present catalyst system.

Full text of DOI:10.1246/cl.2004.632

632
Chemistry Letters Vol.33, No.5 (2004)
A Highly Effective and Practical Biaryl Synthesis with Triallyl(aryl)silanes and Aryl Chlorides
Akhila K. Sahoo, Yoshiaki Nakao, and Tamejiro Hiyamaꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Katsura, Kyoto 615-8510
(Received February 19, 2004; CL-040190)
A general and convenient approach for the palladium-cata-
lyzed cross-coupling of triallyl(aryl)silanes, stable and easily ac-
cessible arylsilanes, with aryl chlorides has been demonstrated.
The scope of the reaction is broad and a wide variety of function-
al groups are tolerant to the present catalyst system.
10 mol %), TBAF (4.0 equiv. with respect to arylsilane) in
THF-H2O (20:1), 80 ꢁC} were applied to a wide array of elec-
tron-poor aryl chlorides to give the corresponding coupled prod-
ucts in good yields (Table 1, Entries 1–3).13 The cross-coupling
proceeded also with electron-rich aryl chlorides (Entries 6 and
7). One or two o-substituents did not affect the efficiency (En-
tries 4, 5, and 8–11). Pyridine- and thiophene-derived heteroaryl
chlorides also cross-coupled smoothly (Entries 12 and 13).
The biaryl subunit has seen a prominent presence not only in
many biologically active molecules but also in many novel ma-
terials such as organic semiconductors and liquid crystals.1 Tran-
sition metal-catalyzed cross-coupling reaction between arylme-
tal nucleophiles with aryl electrophiles has emerged as a
unique and effective strategy to construct biaryls.2 Although var-
ious organometallic reagents have been employed for the cross-
coupling reactions,2,3 the toxic by-products,4 oxygen sensitivity,
and less availability associated with many metallic reagents
makes a great appeal to search for an alternative. To substantiate
these cumulative problems, organosilanes have recently been in-
troduced as a viable candidate due to their availability, stability,
and non-toxic by-products.5
At first, aryl(fluoro)silanes and aryl(chloro)silanes were suc-
cessfully coupled with aryl halides and triflates as disclosed from
this laboratory to provide unsymmetrical biaryls in good yields.6
Recently, this method has been utilized in solid phase synthesis;7
various arylsilanols, trialkoxy(aryl)silanes, poly(phenylsilox-
ane)s, aryl(chloro or fluoro)silacyclobutanes, and arylsilatranes
were employed for the cross-coupling reaction with aryl halides
and triflates.8–10
These arylsilanes, however, require at least one heteroatom
on silicon to enhance the electrophilicity and thus are generally
sensitive to water, base and/or acid. Cross-coupling of arylsi-
lanes have been focused mainly on the reaction with aryl bro-
mides, iodides and triflates; electron-deficient aryl chlorides cou-
ple with aryl(chloro)silanes and phenyltrimethoxysilane partly
successfully, but electron-neutral and -rich aryl chlorides do on-
ly moderately.6,8 To address the above drawbacks, we disclosed
very recently an approach to the cross-coupling of stable all-car-
bon-substituted triallyl(aryl)silanes, as a notable alternative to
the arylsilane nucleophile, easily accessible, quite stable toward
moisture, bases, and acids, with various aryl bromides in the
presence of PdCl2, PCy3, and TBAF in DMSO-H2O to afford
the corresponding biaryls in good to excellent yields.11 Herein,
we describe a general, quite effective, and an alternative method
for the cross-coupling of an array of triallyl(aryl)silanes with
electronically and sterically different aryl chlorides, readily
available with low cost, in fairly good yields.
Table 1. Cross-coupling of triallyl(aryl)silanes with aryl chlo-
rides
1) TBAF (5.0 mmol),
THF–H2O (20 : 1, 5 mL), rt, 1 h.
Ar1-Si(allyl)3
(1.25 mmol)
Ar1 Ar2
2) Ar2-Cl (1.00 mmol)
[(η3-C3H5)PdCl]2 (2.5 mol%)
L (10 mol%), 80 °C
i-Pr
L =
PCy2
i-Pr
i-Pr
Time
/h
Yield of
Ar1–Ar2/%a
Entry
Ar1–
Ar2–
1
2
3
4
5
6
7
8
9
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
4-CF3C6H4–
4-FC6H4–
4-NCC6H4–
2-CF3C6H4–
2-FC6H4–
4-MeOC6H4–
3-MeOC6H4–
2-MeOC6H4–
2-MeC6H4–
1-Naphthyl–
2,6-Me2C6H3–
3-Pyridyl–
3
3
3
3
3
12
14
14
16
14
12
14
12
4
3
6
4
4
4
4
11
95
91
77
86
85
97
99
94
88
94
87
98
10 C6H5–
11 C6H5–
12 C6H5–
13 C6H5–
14 4-MeOC6H4– 4-MeC6H4–
15 4-MeOC6H4– 4-CF3C6H4–
16 4-MeOC6H4– 3-Pyridyl–
17 4-MeC6H4–
18 4-MeC6H4–
19 2-MeC6H4–
20 2-MeC6H4–
21 4-FC6H4–
2-Thienyl–
93
95b
89b
92b
93b
85b
78c
92c
99d
4-MeOC6H4–
2-MeOC6H4–
4-CF3C6H4–
4-MeOC6H4–
4-MeC6H4–
b
aIsolated yield based on aryl chloride. Arylsilane (1.20 mmol)
c
was used. Arylsilane (1.30 mmol) was used. dArylsilane (1.8
equiv. with respect to aryl chloride) was used.
Regardless of the substituent in the arylsilane component,
the cross-coupling proceeds effectively. Thus, chlorine in elec-
tron-rich, -poor chlorobenzenes was successfully substituted
by 4-methoxyphenyl in good yields by the catalyst system (En-
tries 14 and 15). 3-Chloropyridine is not exception (Entry 16).
Triallyl(4-methylphenyl)silane also successfully coupled with
various aryl chlorides (Entries 17 and 18). Further, sterically hin-
Among many trials under various catalyst/ligand/solvent
systems, we were pleased to observe that the catalyst [(ꢀ3-
C3H5)PdCl]2 in the presence of a biaryl ligand introduced by
Buchwald12 played a key role to the cross-coupling reaction.
Thus, our optimized conditions {[(ꢀ3-C3H5)PdCl]2 (2.5 mol
%), 2-dicyclohexylphosphino-20,40,60-triiospropylbiphenyl (L,
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.5 (2004)
633
dered 2-methylphenyl and less nucleophilic 4-fluorophenyl
groups were allowed to couple with a range of aryls in ArCl to
afford the corresponding biaryls in acceptable yields (Entries
19–21).
are highly acknowledged. A. K. S. thanks JSPS for the award
of postdoctoral fellowship.
References and Notes
1
2
3
a) G. Bringmann, W. Rainer, and R. Weirich, Angew. Chem.,
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263 (1998). c) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz,
and M. Lemaire, Chem. Rev., 102, 1359 (2002).
For reviews of metal-catalyzed cross-coupling reactions, see:
a) Top. Curr. Chem., 219 (2002). b) ‘‘Handbook of Organopal-
ladium Chemistry for Organic Synthesis,’’ ed. by E.-I. Negishi,
Wiley-Interscience, New York (2002).
a) K. Tamao, K. Sumitani, and M. Kumada, J. Am. Chem. Soc.,
94, 4374 (1972). b) R. J. P. Corriu and J. P. Masse, Chem.
Commun., 1972, 144. c) J. K. Stille, Angew. Chem., Int. Ed.
Engl., 25, 508 (1986). d) N. Miyaura and A. Suzuki, Chem.
Rev., 95, 2457 (1995).
The efficiency of our strategy is demonstrated by sequential
cross-coupling of polyhalobenzenes. For example, applying dif-
ferent reaction parameters to bromochlorobenzenes, unsymmet-
rical terphenyls are readily prepared. Thus, cross-coupling reac-
tion of triallyl(phenyl)silane (1) with 4-bromochlorobenzene by
the catalyst system including PdCl2, PCy3, and TBAF in DMSO-
H2O afforded the corresponding biaryls without affecting the
chloro group in 98% yield.11 Subsequent cross-coupling with tri-
allyl(4-methoxyphenyl)silane gave the unsymmetrical p-ter-
phenyl in 87% yield as shown in Scheme 1. Similarly, the syn-
thesis of 4-methyl-m-terphenyl was also achieved by
performing the identical reaction sequences with 3-bromochlo-
robenzene in good yields as depicted in Scheme 1.
4
5
For discussions of the toxicity of triorganotin compounds, see:
M. Pereyre, J.-P. Quintard, and A. Rahm, ‘‘Tin in Organic
Synthesis,’’ Butterworth & Co. Ltd. (1987).
a) T. Hiyama, in ‘‘Metal-Catalyzed Cross-Coupling Reactions,’’
ed. by F. Diederich and P. J. Stang, Wiley-VCH, Weinheim
(1998), p 421. b) T. Hiyama and E. Shirakawa, Top. Curr.
Chem., 219, 61 (2002).
Br
(allyl)3Si
Cl
Cl
OMe
1
a, b
c, d
Cl
OMe
Me
6
a) Y. Hatanaka, S. Fukushima, and T. Hiyama, Chem. Lett.,
1989, 1711. b) Y. Hatanaka, K.-i. Gouda, Y. Okahara, and T.
Hiyama, Tetrahedron, 50, 8301 (1994). c) K.-i. Gouda, E.
Hagiwara, Y. Hatanaka, and T. Hiyama, J. Org. Chem., 61,
7232 (1996). d) Y. Hatanaka and T. Hiyama, J. Org. Chem.,
53, 918 (1988). e) T. Huang and C.-J. Li, Tetrahedron Lett.,
43, 403 (2002).
87%
81%
98%
(allyl)3Si
Br
Cl
Me
1
a, b
c, d
93%
Scheme 1. Reagents and Conditions: a. TBAFꢂ3H2O (4.4
equiv.), DMSO-H2O (10:1), rt, 1 h. b. PdCl2 (5 mol %), PCy3
(10 mol %), 80 ꢁC, 12 h. c. TBAFꢂ3H2O (4.4 equiv.), THF-
H2O (20:1), rt, 1 h. d. [(ꢀ3-C3H5)PdCl]2 (2.5 mol %), L (10
mol %), 80 ꢁC, 8 h.
7
8
F. Homsi, K. Hosoi, K. Nozaki, and T. Hiyama, J. Organomet.
Chem., 624, 208 (2001).
a) K. Hirabayashi, J. Kawashima, Y. Nishihara, A. Mori, and T.
Hiyama, Org. Lett., 1, 299 (1999). b) K. Hirabayashi, A. Mori, J.
Kawashima, M. Suguro, Y. Nishihara, and T. Hiyama, J. Org.
Chem., 65, 5342 (2000). c) M. E. Mowery and P. DeShong, J.
Org. Chem., 64, 1684 (1999). d) M. E. Mowery and P. DeShong,
Org. Lett., 1, 2137 (1999). e) K. Shibata, K. Miyazawa, and Y.
Goto, Chem. Commun., 1997, 1309. f) H. N. Lee and S. P.
Nolan, Org. Lett., 2, 2053 (2000). g) A. Mori and M. Suguro,
Synlett, 2001, 845. h) T. Koike and A. Mori, Synlett, 2003,
1850. i) S. Riggleman and P. DeShong, J. Org. Chem., 68,
8106 (2003).
Although the reactive intermediates that were generated on
treatment of TBAF with triallyl(phenyl)silane were not identi-
fied yet, we presume that the three-allyl groups on Si would be
cleaved upon treatment with TBAF and an appropriate amount
of water in the reaction media14 to form possibly activated sili-
cate species such as fluorosilanes, silanepolyols, siloxanes,
and/or their mixed forms.15,16
9
S. E. Denmark and Z. Wu, Org. Lett., 1, 1495 (1999).
In summary, we have demonstrated a general and novel ap-
proach for the cross-coupling of aryl chlorides with triallyl(aryl)-
silanes. It is noteworthy to emphasize that triallyl(aryl)silanes
serve as a highly practical and convenient agent and are fairly
stable toward moisture, acid and/or bases. The catalyst system
described herein effectively runs the cross-coupling of a wide
range of substrates to provide the desired biaryls in excellent
yields. Because of easy accessibility of aryl chlorides and stabil-
ity of organosilane reagents as well as the non-toxic by-products
associated with the triallyl(aryl)silanes, the present methodology
would likely to find a widespread use in synthetic organic chem-
istry. Current efforts are directed towards the practical cross-
coupling of aryl electrophiles by use of activators other than
TBAF.
10 S. E. Denmark and M. H. Ober, Org. Lett., 5, 1357 (2003).
11 Y. Nakao, T. Oda, A. K. Sahoo, and T. Hiyama, J. Organomet.
Chem., 687, 570 (2003).
12 a) J. P. Wolfe, R. A. Singer, B. H. Yang, and S. L. Buchwald, J.
Am. Chem. Soc., 121, 9550 (1999). b) H. N. Nguyen, X. Huang,
and S. L. Buchwald, J. Am. Chem. Soc., 125, 11818 (2003).
13 Reaction of 4-MeOC6H4–I and 4-MeOC6H4–Br with triallyl-
(phenyl)silane (1) under these conditions gave the correspond-
ing coupling products in 77 and 76% yield (GC) respectively.
Stoichiometric reaction of 1 with 4-MeOC6H4–Cl gave 90%
yield (GC) of the product.
14 1H NMR analysis of the reaction mixture showed no detectable
peaks corresponding to allyl groups on silicon upon treatment of
1 with TBAF in THF-H2O at rt for 20 min.
15 a) S. E. Denmark, D. Wehrli, and J. Y. Choi, Org. Lett., 2, 2491
(2000). b) S. E. Denmark and R. F. Sweis, Acc. Chem. Res., 35,
835 (2002).
16 A silicon activating group like 2-Py and benzyl are employed for
the cross-coupling: a) K. Itami, T. Nokami, Y. Ishimura, K.
Mitsudo, T. Kamei, and J.-i. Yoshida, J. Am. Chem. Soc., 123,
11577 (2001). b) B. M. Trost, M. R. Machacek, and Z. T. Ball,
Org. Lett., 5, 1895 (2003).
Financial supports by a Grant-in-Aid for Scientific Research
on Priority Areas ‘‘Reaction Control of Dynamic Complex’’ and
COE Research on ‘‘Elements Science’’, No. 12CE2005 and on
"United Approach to New Material Science’’ from the Ministry
of Education, Culture, Sports, Science and Technology, Japan
Published on the web (Advance View) April 24, 2004; DOI 10.1246/cl.2004.632