Solventless Suzuki coupling reactions on palladium-doped KF/Al2O3

Article abstract of DOI:10.1021/ol990972f

(equation presented) A solventless Suzuki coupling has been developed. A commercially available potassium fluoride-alumina mixture is utilized along with palladium black.

Full text of DOI:10.1021/ol990972f

ORGANIC
LETTERS
1
999
Vol. 1, No. 9
423-1425
Solventless Suzuki Coupling Reactions
on Palladium-Doped KF/Al O
1
2
3
George W. Kabalka,* Richard M. Pagni, and C. Maxwell Hair
Departments of Chemistry and Radiology, The UniVersity of Tennessee at KnoxVille,
KnoxVille, Tennessee 37996-1600
kabalka@utk.edu
Received August 20, 1999
ABSTRACT
A solventless Suzuki coupling has been developed. A commercially available potassium fluoride−alumina mixture is utilized along with palladium
black.
6
The foundation of synthetic organic chemistry rests on the
reaction. Due to our interest in organic reactions carried
ability to form and manipulate carbon-carbon bonds. In
out on alumina surfaces, we decided to investigate carbon-
carbon bond-forming reactions on alumina. The focus of
1
2
7
1972, Kumada and Corriu independently reported that Ni-
(
II) complexes greatly enhanced the rate of reactions of
this study was the development of a novel, solventless Suzuki
coupling methodology incorporating the use of a com-
Grignard reagents with aryl and alkenyl halides. Similar
results were later reported by Murahashi for palladium-
catalyzed coupling reactions. Negishi and co-workers then
mercially available potassium fluoride/γ-alumina mixture,
3
0
KF/Al
2
O
3
, doped with a ligandless Pd catalyst, Scheme 1.
reported an alkynyl transfer from a 1-alkynyl(trialkyl)borate
to iodobenzene through a palladium-catalyzed, addition-
4
,5
elimination sequence analogous to the Heck reaction.
Scheme 1
Boronic esters and acids are thermally stable, relatively
unreactive to both oxygen and water, and thus easily handled
without special precautions. They have been utilized in a
number of carbon-carbon bond-forming reactions, the most
celebrated of which is known as the Suzuki coupling
(
1) (a) Tamao, K.; Sumitani, K.; Kumada M. J. Am. Chem. Soc. 1972,
9
4, 4374. (b) Tamao, K.; Kiso, Y.; Sumitani, K.; Kumada, M. J. Am. Chem.
A number of parameters were investigated. In general, the
Suzuki reactions require the presence of a base, which is
also true of the solid-state reaction (Table 1). Both potassium
phosphate and potassium fluoride were effective in inducing
Soc. 1972, 94, 9268. (c) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet.
Chem. 1973, 50, C12. (d) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise,
T.; Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104,
1
80. (e) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158.
(
(
2) Corriu, R.; Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144.
3) Yamamura, M.; Moritani, I.; Murahashi, S. J. Organomet. Chem.
the solid-phase coupling reactions. Because KF/Al
2 3
O was
commercially available, it was used for the study.
1
975, 23, C39.
4) (a) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.;. Okukado,
(
The quantity of palladium was also found to be important;
a 4-5% loading of palladium worked most efficiently.
Although these levels are significantly higher than the
quantities normally utilized in solution, the ability to recycle
the solid catalyst should lead to more efficient use of the
palladium. The reactions were generally complete in a matter
N. J. Am. Chem. Soc. 1987, 109, 2393. (b) Negishi, E. Aspects of Mechanism
and Organometallic Chemistry; Plenum Press: New York, 1978.
(
5) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic
Press: New York, 1985.
6) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
13. (b) Miyaura, N.; Suzuki, A. Chem ReV. 1995, 95, 2457.
7) Kabalka, G. W.; Pagni, R. M. Tetrahedron 1997, 24, 7999.
(
5
(
1
0.1021/ol990972f CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/29/1999

Table 1. Base Study
Table 3. Boronic Acid Survey
basea
reaction time (h)
yield (%)
NaOH
K2CO3
K3PO4
KF
NaF
Al2O3 (basic)
3
3
3
3
4
6
23
27
71
86
5
0
a
Base (40%) by weight was added to the alumina prior to reactions.
of hours, but the time, as expected, was inversely proportional
to the temperature. For convenience, the reactions were
generally carried out at 100 °C.
Overall, the solid-phase Suzuki reactions were successful
for coupling arylboronic acids to aromatic halides. Reactions
involving alkyl halides (hexyl iodide, butyl iodide, isopropyl
iodide, cyclohexyl iodide, and butyl bromide) or vinyl halides
were unsuccessful, although allylic systems did undergo the
reaction (Table 2). The reaction can also be used to couple
to a powder and then exposed to air over a period of days to
allow for hydration of the surface. Other reagents were
analytical grade and used as received.
The synthesis of 4-methylbiphenyl is representative: To
2 3
a mixture of KF/Al O (0.950 g, 40 wt %) and palladium
black (0.050 g, 0.470 mmol, 99.9+% as a submicron powder)
was added p-methylphenylboronic acid (0.150 g, 1.10 mmol)
contained in a clean, dry, round-bottomed flask. The solid
mixture was stirred at room temperature in the open air until
homogeneous. Iodobenzene (0.209 g, 1.02 mmol) was then
added with stirring. The mixture was stirred at room
temperature for an additional 15-20 min to ensure efficient
mixing.
Table 2. Halide Survey
A condenser was put in place and the flask placed in a
preheated oil bath (100 °C). Stirring was continued during
the entire reaction period. After the allotted time period, the
oil bath was removed and the reaction allowed to cool to
room temperature. A small quantity of hexanes was then
added and the slurry stirred at room temperature for an
additional 20-30 min to ensure product removal from the
surface. The mixture was vacuum filtered through a sintered
glass funnel using Celite as a filter aid. The mixture was
separated via flash chromatography to yield 4-methylbiphenyl
1
(
89%); mp 44.0-45.5 °C; H NMR (CDCl
3
; δ ppm) 7.40
(m, 9H) 2.37 (s, 3H).
The use of KF/alumina as a solid-phase support for
solventless Suzuki reactions offers a convenient, environ-
mentally friendly alternative to traditional reactions. It would
appear that KF is the most effective base. The reactivity
trends observed in solution reactions are also observed in
the solid-state syntheses. That is, organic iodides react faster
than the bromides and chlorides; aryl moieties are more
reactive than alkenyl groups that are themselves more
reactive than alkyl. In addition, the solid-phase syntheses
provide one of the few successful Suzuki methodologies that
can be carried out utilizing ligandless palladium reagents.
Although our studies are not yet complete, the solid-state
aryl iodides to aryl, vinyl, and alkylboronic acids, but the
yields are variable (Table 3).
Requisite boronic acids were prepared via literature
8
procedures. KF/Al
2
O
3
(Aldrich Chemical Co.) was ground
(
8) (a) Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics 1992,
1
1, 652. (b) Brown, H. C.; Scouten, C. G.;. Liotta, R. J. Am. Chem. Soc.
1
979, 101, 96.
1424
Org. Lett., Vol. 1, No. 9, 1999

methodology offers the opportunity to recycle the reagent
via simple filtration) which has significant commercial
appeal.
Acknowledgment. We thank the U.S. Department of
Energy and the Robert H. Cole Foundation for their support.
OL990972F
(
Org. Lett., Vol. 1, No. 9, 1999
1425