Table 2. Pd-Catalyzed Cross-Coupling Reaction of
1,2-Dibromoethane with Arylboronic Acidsa
Figure 1. Effects of substituents on aryl boronic acids p-XC6H4B-
(OH)2 (X ) MeO, Me, H, Cl and CF3). Y ) -1.263x - 0.0476.
R2 ) 0.995
similar yield compared with its para-substituted analogue
(entries 1 and 7, Table). A reasonable yield was achieved
when the protocol was applied to a more sterically demand-
ing substrate, 2,4,6-trimethylphenyl boronic acid (54%
isolated yield). 2-Vinyl-6-methoxynaphthalene, a key inter-
mediate for the production of Naproxen in the Albermale
process, was obtained in 66% isolated yield (entry 10, Table
2).1c
The dependence of the substitution on the aryl boronic
acid para position is also evidenced in a competitive
experiment (Figure 1). A plot of the relative reactivity of
substituted aryl boronic acids against the σ constant shows
that the relative reactivity is sensitive to the electronic effects
of the substituents on the aryl boronic acids. The reactivity
is opposite to those observed for cross-coupling reactions
with aryl halides such as Heck13 and Suzuki14 reactions,
where higher activites are obtained with aryl halides pos-
sesing electron-withdrawing groups in the para position. Aryl
boronic acids containing electron-donating groups in the para
position are more reactive and the correlation yields a value
of F ) -1.26. The effect is different from those obtained
for the Ni-catalyzed Suzuki cross-coupling of aryl boronic
acids with aryl chlorides15 and aryl tosylates,16 indicating
that oxidative addition is not the rate-determining step.
Higher reaction rates for electron-donating substituents in
the aryl boronic acid have also been observed for the Pd-
catalyzed homocoupling of arylboronic acids.17 To explain
this behavior, the authors proposed that the transfer of the
aryl group to the electron-deficient palladium should be
favored by the electron-donating ability of the substituent.
The Hammet correlation observed in our case can also be
explained by the enhancement of the nucleophilicity of the
a Reaction conditions: (1) Dehydrobromination: 1 mmol of BrCH2CH2Br,
4 mmol of KOH, THF (2.5 mL), 100 °C, 1 h. (2) Cross-coupling reaction:
1.5 mmol of ArB(OH)2, 0.04 mmol of Pd(OAc)2, 0.08 mmol of PPh3, MeOH
(2.5 mL), 100 °C, 1 h. b GC yields (isolated yields are given in parentheses).
interesting to note that a lower yield was achieved (25%)
when the reaction with 1-naphthylboronic acid was carried
out in a open reflux setup. Aryl boronic acids containing
electron-donating groups in the para position (entries 1 and
2, Table 2) are efficiently coupled to provide the correspond-
ing vinyl arenes in excellent yields. Lower yields were
obtained with aryl boronic acids containing electron-
withdrawing groups in the para position (entries 3-6, Table
2). ortho-Methoxy-substituted phenyl boronic acid gave a
(12) In a typical experiment, an oven-dried resealable Schlenk flask was
evacuated and back-filled with argon and charged with KOH (225 mg, 4
mmol). The flask was evacuated and back-filled with argon, and then
tetrahydrofuran (2.5 mL) and 1,2-dibromoethane (87 µL, 1 mmol) were
added. The reaction mixture was stirred at 100° for 1 h. The solution was
then allowed to cool to room temperature, and 1-naphthylboronic acid (258
mg, 1.5 mmol), PPh3 (21 mg, 0.08 mmol), Pd(OAc)2 (9.0 mg, 0.04 mmol),
and methanol (2.5 mL) were added. The reaction mixture was stirred at
100 °C for 1 h. The solution was then allowed to cool to room temperature,
taken up in ether (20 mL), and washed with aqueous NaOH (1 M, 5 mL)
and brine (2 × 5 mL). The organic layer was dried over MgSO4, filtered,
and concentrated in vacuo, and then the crude material was purified by
flash chromatography on silica gel.
(13) (a) Weiss, H.; Milstein, D. Chem. Commun. 1999, 1901. (b) Bohm,
V. P. W.; Hermann, W. A. Chem. Eur. J. 2001, 7, 4191. (c) Consorti, C.
S.; Zanini, M. L.; Leal, S.; Eberling, G.; Dupont, J. Org. Lett. 2003, 5,
983.
(14) Zim, D.; Gruber, A. S.; Ebeling, G.; Dupont, J.; Monteiro, A. L.
Org. Lett. 2000, 2, 2881.
(15) Saito, S.; Oh-tani, S.; Miayura, N. J. Org. Chem. 1997, 62, 8024.
(16) Zim, D.; Lando, V. R.; Dupont, J.; Monteiro, A. L. Org. Lett. 2001,
3, 3049.
(17) Moreno-Mana˜s, M.; Pe´rez, M.; Pleitxats, R. J. Org. Chem. 1996,
61, 2346.
Org. Lett., Vol. 5, No. 16, 2003
2893