TABLE 1. Reaction of Organic Halides with R3SiH in
represents an interesting challenge in the field of organic
synthesis.5,9
a
the Presence of a Catalytic Amount of Pd(t-Bu3P)2
Our group and others have recently demonstrated that
palladium catalysts coordinated with bulky, electron-rich
tri-tert-butylphosphine can exhibit high reactivity in a
range of coupling processes.10-12 During the course of our
study, we found that trialkylsilanes show different reac-
tivity toward aryl halides in the presence versus the
absence of Pd(t-Bu3P)2 (Scheme 2, route d; silylation).13
In this report, I attempt to describe the palladium-
catalyzed silicon-aryl bond formation using aryl iodides
with hydrosilanes in the presence of a catalytic amount
of Pd(t-Bu3P)2 and provide the information on the scope
and limitations of this reaction.
The coupling reaction of 4-iodoanisole with triethylsi-
lane was selected to optimize the reaction conditions. It
was found that, among the catalysts tested, Pd(t-Bu3P)2
was the most effective palladium source.14a The reaction
proceeded smoothly even at 1 mol % catalyst loading.
After screening bases, we recognized K3PO4 as the most
effective.14b The desired silylated product was obtained
in low yield, and the reduced one was dominantly
observed without base. Among the solvents examined,
the use of 1-methyl-2-pyrrolidinone (NMP) was essential
for this silylation. Room temperature was found to be
optimal for the reaction. The optimized conditions were
4-iodoanisole (1.0 equiv), triethylsilane (1.1 equiv), K3PO4
as base (3.0 equiv),14c and 1 mol % of Pd(t-Bu3P)2 in NMP
at room temperature under a nitrogen atmosphere, which
afforded the silyl product in an 84% isolated yield along
with a small amount of anisole (ca. 10%).15
a Reaction conditions: aryl halide 0.55 mmol, R3SiH 0.60 mmol,
K3PO4 1.65 mmol, Pd(t-Bu3P)2 0.0055 mmol, NMP 1 mL. b Isolated
yield of silylated product. Other major products were reduction
ones, and the GC yield is shown in parentheses. c Starting material
was recovered in 61% (GC yield). d The silylated product could not
be detected by GC-MS. e GC yield. The silylated product could
be detected by GC-MS, but could not be isolated. f The reaction
time was 60 h.
To clarify the generality and scope of this coupling
reaction, the silylations of a wide variety of aryl halides
(9) Quite recently, Tsukada and Hartwig reported the direct sily-
lation of benzene with triethylsilane in the presence of platinum
complex. See: Tsukada, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005,
127, 5022.
(10) For recent reviews, see: (a) Fu, G. C. J. Org. Chem. 2004, 69,
3245. (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176.
(11) (a) Suzuki reaction: Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 1998, 37, 3378. (b) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem.
Soc. 2000, 122, 4020. (c) Heck reaction: Littke, A. F.; Fu, G. C. J. Org.
Chem. 1999, 64, 10. (d) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001,
123, 6989. (e) Stille reaction: Littke, A. F.; Fu, G. C. Angew. Chem.,
Int. Ed. 1999, 38, 2411. (f) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am.
Chem. Soc. 2002, 124, 6343. (g) Sonogashira reaction: Hundertmark,
T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729.
(g) Negishi reaction: Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123,
2719.
and trialkylsilanes were examined under these condi-
tions. The results are summarized in Table 1. The
electronic and steric characteristics of the substrates
significantly affected the reactions. Aryl iodides were
significantly more reactive than bromides and chlorides
(entries 1, 4, and 5). The presence of an electron-
withdrawing group on the aromatic ring interfered with
the coupling reaction (entry 6). On the other hand,
electron-rich aryl iodide afforded moderate to good prod-
uct yields (entries 1, 8, and 10), although the prolonged
reaction time was required for meta-substituted aryl
iodide (entry 12).16,17 This is in contrast to a typical
palladium-catalyzed cross-coupling process, where electron-
rich aryl halide furnished lower product yields. Addition-
ally, the presence of a group at the ortho-position of the
aromatic ring afforded no silylated product due to the
steric hindrance (entry 7). This reaction was applicable
(12) For a pioneering study on the use of t-Bu3P in palladium-
catalyzed coupling reactions, see: (a) Nishiyama, M.; Yamamoto, T.;
Koie, Y. Tetrahedron Lett. 1998, 39, 617. (b) Yamamoto, T.; Nishiyama,
M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367. (c) Watanabe, M.;
Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1999, 40, 8837. (d) Wa-
tanabe, M.; Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett.
2000, 41, 481.
(13) Pd(t-Bu3P)2 is available from Strem Chemicals (catalog number
46-0252).
(14) Notes: (a) The yields of the silylation of 4-iodoanisole with
triethylsilane in the presence of other palladium catalysts (1 mol %)
and K3PO4 (3.0 equiv) are as follows. Pd(PPh3)4: trace, PdCl2(PPh3)2:
trace, and Pd[(C6H11)3P]2: 56% (Pd[(C6H11)3P]2 is available from Strem
Chemicals, catalog number 46-0260). (b) The yields of the silylation of
4-iodoanisole with triethylsilane in the presence of Pd(t-Bu3P)2 (1 mol
%) and other bases (3.0 equiv) are as follows. Et3N: 47%, i-Pr2NEt:
59%, K2CO3: 80%, Na2CO3: 75%, KOAc: 34%, and without base: 29%.
(c) The yields of the silylation of 4-iodoanisole with triethylsilane in
the presence of Pd(t-Bu3P)2 (1 mol %) and K3PO4 (x equiv) are as
follows. 1.0 equiv: 26%, 2.0 equiv: 59%, 3.0 equiv: 84%, and 4.0
equiv: 82%.
(16) 4-Iodo-N,N-dimethylaniline was prepared from 4-iodoaniline by
reductive methylation with formaldehyde and NaBH3CN in the
presence of acetic acid. (a) Jian, H.; Tour, J. M. J. Org. Chem. 2003,
68, 5091. (b) Giumanini, A. G.; Chiavari, G.; Musiani, M. M.; Rossi, P.
Synthesis 1980, 9, 743.
(17) Note: On a 20 mmol scale, the silylation depicted in entry 8 of
Table 1 proceeds in 73% yield (3.45 g of product). See Supporting
Information for detailed preparation.
(15) The yield of anisole was estimated by GC-MS using an internal
standard.
9608 J. Org. Chem., Vol. 70, No. 23, 2005