-donating groups exhibit similar reactivity (entries 4 and 6),
(2) the steric effect of ortho substituents is minimal (cf.
entries 1 and 4-7) except in the case of the 2-carbomethoxy
group (entry 3) were chelation between the carbonyl moiety
and the palladium may slow the reductive elimination step,
(3) the reaction tolerates diverse functionalities such as ester,
nitro, cyano (vide infra), ether, and even hydroxyl.
Scheme 1
The mild reaction conditions and uniformly high yields
compare favorably with other methods to produce these
compounds. For example, 2e has been previously prepared
using a Stille coupling.8 The conditions were considerably
more vigorous requiring 2 h in refluxing acetonitrile to
produce 2e in 80% yield. The silanol coupling described
herein was complete in 10 min at room temperature and gave
the same yield of the product. Furthermore, compound 2g
has been obtained in 55% yield from 2-bromobenzyl alcohol
by use of an organostannane-based cross-coupling method.9
The optimization of the palladium(0)-catalyzed cross-
coupling was guided by our previous studies with alkenyl-
silanols.3c Accordingly, silanol 1 was first combined with a
1.0 M solution of tetrabutylammonium fluoride (TBAF‚
3H2O, Fluka) in THF at room temperature, followed by the
addition of the aryl iodide and the palladium complex (Pd-
(dba)2). We were delighted to find that the reactions were
clean and generally complete within 10-20 min. However,
as had been noted previously, we encountered difficulties
in the purification step because (1) the polarity of the
products was similar to the dba ligand and to the polysilicone
byproducts and (2) the products were found to be particularly
labile in air and on chromatographic media. Moreover,
reverse-phase (C-18) silica chromatography was either not
efficient or led to partial decomposition of the products if
long gradient elutions were used. By using rapid silica gel
column chromatography, we were able to separate the
polysilicone byproducts, but the product was always con-
taminated with dba. By the simple expedient of replacing
the Pd(dba)2 catalyst with [allylPdCl]2, we were able to
secure 2 in an analytically pure form.
The cross-coupling of 1 with an alkenyl electrophile, ethyl
(E)-3-iodoacrylate, was also briefly examined (Scheme 2).
Scheme 2
With a viable protocol in hand, the scope of the reaction
was further investigated with aryl iodides bearing electron-
withdrawing or -donating groups in para, meta, or ortho
positions (Table 1). For all aryl iodides examined, the
The reaction rate and yield were comparable to that obtained
with aryl iodides, and after 2 h, 3 could be isolated in 81%
yield after Al2O3 chromatography. The corresponding (Z)-
3-iodoacrylate suffered decomposition under the reaction
conditions and did not lead to coupling.
Table 1. Palladium-Catalyzed Cross-Coupling of 1 with Aryl
Iodidesa
Having demonstrated that [2-(5,6-dihydro-4H-pyranyl)]-
dimethylsilanol serves efficiently in the cross-coupling
reaction, we next investigated other R-alkoxyvinyl donors
such as a dihydrofuran and butoxy vinyl ether. Following
on the successful coupling of silanol 1, we first considered
the use of (1-butoxyvinyl)dimethylsilanol and [2-(4,5-dihy-
drofuranyl)]dimethylsilanol. Unfortunately, the sequence
established for the synthesis of 1 (lithiation of the vinyl group
and subsequent quenching with D3) did not provide the
silanols cleanly.10 Previous experience with handling silanols
suggested that increasing the bulk of the silicon substituent
could make the products more tractable.3c Since hexaiso-
entry
R
time, min
product
yield,b %
1
2
3
4
5c,d
6
7c,d
8
4-CO2Et
3-CO2Et
2-CO2Me
2-NO2
10
10
240
10
20
10
2a
2b
2c
2d
2e
2f
84
86
92
85
80
74
88
87
2-CH3
2-OCH3
2-CH2OH
3-CH2OAc
(7) (a) Sieburth, S. McN.; Mu, W.J. Org. Chem. 1993, 58, 6314-6318.
(b) Sieburth, S. McN.; Fensterbank, L. J. Org. Chem. 1993, 58, 7584-
7586.
20
20
2g
2h
(8) Macleod, D.; Moorcroft, D.; Quayle, P.; Dorrity, M. R. J.; Malone,
J. F.; Davies, G. M. Tetrahedron Lett. 1990, 31, 6077-6080.
(9) Spirocyclization of compound 2g was observed, when dissolved in
“aged” CDCl3: Elsley, D. A.; Macleod, D.; Miller, J. A.; Quayle, P.; Davies,
G. M. Tetrahedron. Lett 1992, 33, 409-412.
a All reactions employed 1.2 equiv of 1. b Yield of analytically pure
materials. c Yield of chromatographically homogeneous materials. d 1.2
equiv of 1 and 5 mol % of Pd(dba)2 were used.
(10) Mori has reported the synthesis of [2-(4,5-dihydrofuranyl)]dimeth-
ylsilanol using D3, but in our hands the procedure failed to give pure
product: Hirabayashi, K.; Takahisa, E.; Nishihara, Y.; Mori, A.; Hiyama,
T. Bull. Chem. Soc. Jpn. 1998, 71, 2409-2417.
reaction proved to be fast and high yielding. Several features
of the reaction are noteworthy: (1) electron-withdrawing or
3222
Org. Lett., Vol. 2, No. 20, 2000