ORGANIC
LETTERS
2004
Vol. 6, No. 9
1421-1424
Pd2(dba)3/P(i-BuNCH CH ) N-Catalyzed
Stille Cross-Coupling of Aryl Chlorides
2
2 3
Weiping Su, Sameer Urgaonkar, and John G. Verkade*
Department of Chemistry, Gilman Hall, Iowa State UniVersity, Ames, Iowa 50011
Received March 4, 2004
ABSTRACT
The Pd2(dba)3/P(i-BuNCH CH ) N (1d) catalyst system is highly effective for the Stille cross-coupling of aryl chlorides with organotin compounds.
2
2 3
This method represents only the second general method for the coupling of aryl chlorides. Other proazaphosphatranes possessing benzyl
substituents also generate very active catalysts for Stille reactions. Noteworthy features of the method are: (a) commercial availability of
ligand 1d, (b) the wide array of aryl chlorides that can be coupled, and (c) applicability to aryl, vinyl, and allyl tin reagents.
The palladium-catalyzed Stille cross-coupling of aryl halides
(or halide equivalents) with organotin reagents is an impor-
tant C-C bond-forming reaction that has found wide
application in organic synthesis.1,2 Until recently, this method
was handicapped by the need to use aryl bromides or iodides
as the reaction partner. Unlike the case with other Pd-
catalyzed processes (e.g., Suzuki3 and Buchwald-Hartwig
amination4 reactions) where a myriad of catalyst systems
allow coupling of economically attractive but notoriously
unreactive aryl chlorides, the same is not true with the Stille
coupling of aryl chlorides.5 However, significant progress
was achieved recently. For example, Fu,6 in his pioneering
studies, disclosed a palladium-catalyst based on sterically
hindered electron-rich P(t-Bu)3 for the Stille cross-coupling
of aryl chlorides. This method, although general, requires a
highly air-sensitive and pyrophoric ligand that requires
special handling techniques. Although the air-stable Pd[P(t-
Bu)3]27 complex was recommended as an alternative to Pd2-
(dba)3/P(t-Bu)3 for this process, its high cost is a deterrent
to its widespread use. On the other hand, P(t-Bu)3 has
recently become commercially available as the air-stable
precursor [(t-Bu)3PH]BF4.8 Nolan9 reported a Pd/N-hetero-
cyclic carbene system for the Stille reaction of aryl chlorides.
However, this protocol provided good yields only for
(1) For reviews on Stille cross-coupling reaction, 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) Littke, A. F.; Fu, G. C. Angew
Chem., Int. Ed. 2002, 41, 4176.
(2) For applications of the Stille reaction in natural product synthesis,
see: (a) Nicolaou, K. C.; Li, Y.; Sugita, K.; Monenschein, H.; Guntupalli,
P.; Mitchell, H. J.; Fylaktakidou, K. C.; Vourloumis, D.; Giannakakou, P.;
O’Brate, A. J. Am. Chem. Soc. 2003, 125, 15443. (b) Kadota, I.; Takamura,
H.; Sato, K.; Ohno, A.; Matsuda, K.; Yamamoto, Y. J. Am. Chem. Soc.
2003, 125, 46. (c) Boger, D. L.; Ichikawa, S.; Jiang, H. J. Am. Chem. Soc.
2000, 122, 12169.
(3) For leading references to Suzuki couplings of aryl chlorides, see:
(a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722. (b) Littke, A. F.; Fu, G. C. Angew Chem., Int. Ed. 1998, 37,
3387. (c) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020. (d) Bedford, R. B.; Cazin, C. S. J. Chem. Commun. 2001, 1540. (e)
Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513. (f) Herrmann, W. A.;
Reisinger, C.-P.; Spiegler, M. J. Organomet. Chem. 1998, 557, 93. (g)
Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64,
3804. (h) Urgaonkar, S.; Nagarajan, M. Verkade, J. G. Tetrahedron Lett.
2002, 43, 8921.
(4) For leading references to Buchwald-Hartwig amination reactions
of aryl chlorides, see: (a) Wolfe, J. P.; Tomori, J.; Sadighi, J. P.; Yin, J.;
Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (b) Hartwig, J. F.;
Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M.
J. Org. Chem. 1999, 64, 5575. (c) Huang, J.; Grasa, G. A.; Nolan, S. P.
Org. Lett. 1999, 1, 1307. (d) Nishiyama, M.; Yamamoto, T.; Koie, Y.
Tetrahedron Lett. 1998, 39, 2367. (e) Bei, X.; Uno, T.; Norris, J.; Turner,
H. W.; Weinberg, W. H.; Guram, A. S.; Petersen, J. L. Organometallics
1999, 18, 1840. (f) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998,
120, 7369. (g) Reddy, N. P.; Tanaka, M.; Tetrahedron Lett. 1997, 38, 4807.
(h) Urgaonkar, S.; Nagarajan, M.; Verkade, J. G. Org. Lett. 2003, 5, 815.
(5) For Pd-catalyzed Stille reactions of activated aryl chlorides, see:
Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 301.
See also refs 1b and 1c.
(6) (a) Littke, A. F.; Fu, G. C. Angew Chem., Int. Ed. 1999, 38, 2411.
(b) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343.
(7) Available from Strem Chemicals.
(8) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295.
(9) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119.
10.1021/ol0495927 CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/01/2004