1
20
M. Murata et al.
LETTER
(
X = Br) were not particularly large. It is noteworthy that Acknowledgment
the reactions of both of heteroaryl and di-ortho-substitut-
ed bromides, which were problematic substrates in previ-
ous phosphine-based catalyst systems, proceeded in high
This work is supported by a Grant-in-Aid for Encouragement of
Young Scientists (B) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan (No. 16750069). Additional
4
b,c
yields (entries 1–3).
In all cases listed in Table 2, financial support by the Akiyama Foundation, and Taisho Pharma-
homo-coupling of neither of the reactants was detected, ceutical Co., Ltd. Award in Synthetic Organic Chemistry from The
Society of Synthetic Organic Chemistry, Japan, is gratefully ack-
nowledged.
although small amount of reduced by-product was pro-
duced occasionally.
As aryl chlorides 2 (X = Cl) are often more readily avail-
able and less expensive than their bromide and iodide
References and Notes
counterparts, much attention has been focused on the cou-
pling reaction of aryl chlorides. In the fluoride-induced
cross-coupling of aryltrialkoxysilanes 1, however, high
(
1) For reviews, see: (a) Stille, J. K. Angew. Chem., Int. Ed.
Engl. 1986, 25, 508. (b) Farina, V.; Krishnamurthy, V.;
Scott, W. J. Org. React. 1997, 50, 1. (c) Mitchell, T. N. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.;
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998, 167.
2) For reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev.
9
catalyst loading was required for the coupling using Buch-
4
c
wald’s ligand system, and N-heterocyclic carbenes sys-
tem was not suitable for electron-neutral aryl chlorides.4d
Gratifyingly, the present catalyst system also proved to be
highly efficient for electron-neutral and electron-deficient
aryl chlorides (entries 9 and 10). In contrast, electron-do-
nating or ortho-substituents prevented complete conver-
sion although nearly good to moderate yields were still
obtained (entries 11 and 12).
(
1995, 95, 2457. (b) Suzuki, A. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998, 49. (c) Miyaura, N. Adv.
Organomet. Chem. 1998, 6, 187.
(3) For reviews, see: (a) Hatanaka, Y.; Hiyama, T. Synlett 1991,
45. (b) Hiyama, T. In Metal-Catalyzed Cross-Coupling
8
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998, 421. (c) Hiyama, T.; Shirakawa, E. Top.
Curr. Chem. 2002, 219, 61.
In conclusion, we have developed a general method for
cross-coupling of aryltrialkoxysilanes with aryl halides
(4) (a) Shibata, K.; Miyazawa, K.; Goto, Y. Chem. Commun.
1997, 1309. (b) Mowery, M. E.; DeShong, P. J. Org. Chem.
1999, 64, 1684. (c) Mowery, M. E.; DeShong, P. Org. Lett.
1999, 1, 2137. (d) Lee, H. M.; Nolan, S. P. Org. Lett. 2000,
2, 2053. (e) Murata, M.; Shimazaki, R.; Watanabe, S.;
using Pd(dba) /i-Pr-DPEphos (L8) as the catalyst. It is
2
noteworthy that the formation of homo-coupled by-prod-
ucts can be almost completely suppressed. In addition, the
substrate scope is significantly broader than previous
methods and includes heteroaryl and sterically-hindered
aryl halides. Further studies are currently underway to ex-
pand the scope of organic electrophiles.
Masuda, Y. Synthesis 2001, 2231. (f) Wolf, C.; Lerebours,
R. Org. Lett. 2004, 6, 1147. (g) Lerebours, R.; Wolf, C.
Synthesis 2005, 2287.
(5) For the synthetic route to aryltrialkoxysilanes, see:
(
a) Murata, M.; Suzuki, K.; Watanabe, S.; Masuda, Y. J.
Palladium-Catalyzed Biaryl Coupling – General Procedure
Org. Chem. 1997, 62, 8569. (b) Manoso, A. S.; DeShong, P.
J. Org. Chem. 2001, 66, 7455. (c) Murata, M.; Ishikura, M.;
Nagata, M.; Watanabe, S.; Masuda, Y. Org. Lett. 2002, 4,
1843. (d) Komuro, K.; Ishizaki, K.; Suzuki, H. Touagousei-
kenkyu-nenpo 2003, 6, 24.
(
Table 2)
In a glove box, Pd(dba) (15 mmol), i-Pr-DPEphos (L8, 20 mmol),
2
and TBAF·3H O (0.60 mmol) were placed into a screw-capped vial,
2
and dissolved in 0.5 mL of toluene. After being stirred for 20 min,
aryl halide 2 (0.50 mmol) and aryltrialkoxysilane 1 (0.60 mmol)
were added successively. The vial was sealed with a cap and
removed from the glove box. The reaction mixture was then stirred
at 80–110 °C for 18 h. After the reaction, the mixture was diluted
with Et O, washed with H O, and dried over Na SO . The solvent
(6) For modified Negishi biaryl coupling using DPPF ligand,
see: Gauthier, D. R. Jr.; Szumigala, R. H. Jr.; Dormer, P. G.;
Armstrong, J. D. III; Volante, R. P.; Reider, P. J. Org. Lett.
2002, 4, 375.
7) For Suzuki–Miyaura biaryl coupling using DPEphos ligand,
see: Yin, J.; Rainka, M. P.; Zhang, X.-X.; Buchwald, S. L. J.
Am. Chem. Soc. 2002, 124, 1162.
(
2
2
2
4
was removed under reduced pressure, and the residue was purified
by flash column chromatography to give the desired biaryl 3.
(
8) i-Pr-DPEphos (L8) was prepared from diphenylether and
(
i-Pr) PCl by a similar procedure for the preparation of
2
DPEphos. See: Kranenburg, M.; Vanderburgt, Y. E. M.;
Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Goubitz, K.;
Fraanje, J. Organometallics 1995, 14, 3081.
(9) For a review on palladium-catalyzed couplings of aryl
chlorides, see: Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed.
2002, 41, 4176.
Synlett 2006, No. 1, 118–120 © Thieme Stuttgart · New York