Microwave enhanced cross-coupling reactions involving alkenyl- and alkynyltrifluoroborates

Article abstract of DOI:10.1016/j.tetlet.2005.12.025

Cross-coupling reactions of potassium arylvinyltrifluoroborates with aryl iodides in the presence of a palladium catalyst occur rapidly utilizing microwave irradiation. The coupled products are produced in excellent yields. Alkynyltrifluoroborates also undergo the coupling reaction.

Full text of DOI:10.1016/j.tetlet.2005.12.025

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1133–1136
Microwave enhanced cross-coupling reactions involving
alkenyl- and alkynyltrifluoroborates
George W. Kabalka,* Mohammad Al-Masum,ꢀ Arjun R. Mereddy and Eric Dadush
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 22 August 2005; revised 5 December 2005; accepted 6 December 2005
Available online 27 December 2005
Abstract—Cross-coupling reactions of potassium arylvinyltrifluoroborates with aryl iodides in the presence of a palladium catalyst
occur rapidly utilizing microwave irradiation. The coupled products are produced in excellent yields. Alkynyltrifluoroborates also
undergo the coupling reaction.
Ó 2005 Published by Elsevier Ltd.
It has been well documented that palladium catalyzed
cross-coupling reactions between organoboron com-
pounds and organic halides (as well as triflates) are pow-
erful tools for the formation of carbon–carbon bonds.1
There are, however, problems specific to alkenylboronic
acids and esters in the Suzuki–Miyaura coupling reac-
tions. For example, vinylboronic acids can be lost to
polymerization. Furthermore, vinylboronic esters are
not always selective in cross-coupling reactions, yielding
mixtures of Suzuki–Miyaura and Heck coupled prod-
ucts.2 Recent studies have revealed that potassium alken-
yltrifluoroborates and alkynyltrifluoroborates offer
solutions to a number of problems that occur in organo-
boron coupling reactions.3 We have begun to explore
the use of microwave irradiation as an alternative to
thermal heating in reactions using potassium organo-
trifluoroborates. The use of microwaves in organic
synthesis has gained importance in organic chemistry
in recent years.4 We recently reported the first use
of microwaves in cross-coupling reactions involving
potassium aryltrifluoroborates.5 In the course of those
studies, we developed a microwave assisted, palladium
catalyzed cross-coupling reaction of potassium vinyltri-
fluoroborates with aryl halides. In this letter, we report
the results of this study, coupling reactions that can be
used to prepare a variety of stilbenes in excellent yields
in less than ten minutes (Scheme 1).
The photochemistry and physics of stilbenes have been
the subject of numerous investigations. In medicine, stil-
bene derivatives have proven to be antioxidants.6 They
also have important applications in macromolecular
chemistry and nanoscience.7
The scope of the reaction was investigated by allowing
potassium phenylvinyltrifluoroborate, 1, to react with
various substituted iodobenzenes (Table 1). A catalyst
loading of 2 mol % PdCl2(dppf)CH2Cl2, along with
Cl
BF3K
2 mole %PdCl2(dppf)CH2Cl2
I
Cl
+
i-PrOH-H2O (2:1), i-Pr2NEt
MW, 100 oC, 10 min
99 %
3
1
2
Scheme 1.
Keywords: Alkenyltrifluoroborates; Alkynyltrifluoroborates; Microwave irradiation.
*
ꢀ
Corresponding author. Tel.: +1 865 974 3260; fax: +1 865 974 2997; e-mail: kabalka@utk.edu
Present address: Department of Chemistry, Tennessee State University, Nashville, TN 37209, USA.
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.12.025

1134
G. W. Kabalka et al. / Tetrahedron Letters 47 (2006) 1133–1136
Table 1. Microwave enhanced cross-coupling reaction of potassium
trans-2-phenylvinyltrifluoroorate, 1 with iodobenzenesa
3.0 equiv of Hunigꢁs base (i-Pr NEt), in isopropanol/
¨
2
water (2:1) was found to provide the coupled products
in good to excellent yields.8 In the absence of a palla-
dium catalyst, no coupling product was observed. The
reactions are very straightforward stereoselective and
relatively insensitive to the nature of the substituents.
Reagents containing electron withdrawing groups
(Table 1, entries 2–5), electron donating groups (Table
1, entries 6–8) all provide the cross-coupled styrene
products in high yields. Having successfully utilized
microwaves to enhance Suzuki coupling of potassium
trans-2-phenylvinyltrifluoroborate with aryl halides, we
then investigated the use of other substituted potassium
arylvinyltrifluoroborates (Table 2). All reactants pro-
vided the cross-coupled stilbene products in excellent
yields (Table 2, entries 1–6). An aliphatic vinyltrifluoro-
borate also readily participated in the reaction (Table 2,
entry 7). Yields were generally somewhat lower for
coupling reactions involving the alkynyl trifluoro-
borates; a situation also noted in thermal coupling
reactions3f (Table 2, entries 8–13).
Entry Aryl iodide, 2
Product, 3
Yield
(%)
3a
2a
1
2
3
67
61
99
I
Ph
F
F
2b
2c
3b
I
I
Ph
Ph
Cl
Cl
3c
COCH3
COCH3
4
5
91
76
3d
2d
I
I
Ph
Ph
3e
2e
NO
NO
2
2
The reactions are rapid and simple to perform. In a typ-
ical experiment, the organotrifluoroborate9 (0.50 mmol)
and palladium catalyst (0.01 mmol) are placed in an
argon flushed pyrex tube. The aryl halide (0.50 mmol)
is then added along with diisopropyl ethyl amine
(1.5 mmol) and 5 mL of isopropanol/water (2:1). The
pyrex tube is capped with a rubber septum and placed
in a CEM microwave unit and allowed to react at
100 °C for 10 min. The product is worked up by adding
water (15 mL) and ether (15 mL), the ether layer sepa-
rated, the solvent extracted, and the product isolated
by column chromatography. The product yields gener-
ally exceed those obtained in the thermal reactions by
ꢀ10%3i whereas the coupling yields are similar for ther-
mal reactions generating alkyne products.3j,k
3f
2f
6
7
8
79
96
92
Ph
I
OCH
CH3
OCH3
3
CH
CH3
3
3g
2g
I
I
Ph
Ph
CH
3
2h
3h
CH
CH
3
3
a All yields are of pure products isolated by silica gel chromatography.
Table 2. Microwave enhanced cross-coupling reactions for the synthesis of styrenes and enynesa
Productb
Yields (%)
R
Entry
Aryl iodide
BF3K
Cl
BF3K
BF3K
BF3K
Cl
1
92
CF3
CF3
CF3
Cl
I
I
CF3
CF3
2
3
4
81
95
87
NO2
NO2
COCH3
COCH3
I
I
CF3
Cl
BF3K
BF3K
NO2
NO2
OCH3
OCH3
5
85
Cl
I
Cl

G. W. Kabalka et al. / Tetrahedron Letters 47 (2006) 1133–1136
1135
Table 2 (continued)
Entry
Aryl iodide
Productb
Yields (%)
R
BF3K
Cl
BF3K
Cl
F
6
7
8
94
91
60
CH3
I
I
I
CH3
F
BF3K
C7H15
C7H15
F
BF3K
F
Cl
9
65
68
72
69
52
CH3
BF3K
CH3
Cl
I
I
I
Cl
10
11
12
13
CH3O
CH3O
CH3O
NC
BF3K
CH3O
CH3O
CH3O
NC
Cl
Br
O
BF3K
BF3K
Br
O
I
I
O
O
BF3K
a All yields are of pure products isolated by silica gel chromatography.
b Satisfactory combustion analyses were obtained for all new compounds.10
F. Tetrahedron Lett. 2004, 45, 3471; (c) Molander, G. A.;
Ribagorda, M. J. Am. Chem. Soc. 2003, 125, 11148; (d)
Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 1381; (e)
Molander, G. A.; Bernardi, C. R. J. Org. Chem. 2002, 67,
8424; (f) Molander, G. A.; Katona, B. W.; Machrouhi, F.
J. Org. Chem. 2002, 67, 8416; (g) Pucheault, M.; Darses,
S.; Genet, J.-P. Eur. J. Org. Chem. 2002, 3552; (h)
Molander, G. A.; Rivero, M. R. Org. Lett. 2002, 4, 107;
(i) Batey, R. A.; Thadani, A. N.; Smil, D. V.; Lough, A.
Synthesis 2000, 990; (j) Darses, S.; Michauld, G.; Genet,
J.-P. Eur. J. Org. Chem. 1999, 1875; (k) Stefani, H. A.;
Cella, R.; Dorr, F. A.; Pereira, C. M.; Zeni, G.; Fome, L.
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Acknowledgments
We wish to thank the Department of Energy and the
Robert H. Cole Foundation for support of this research.
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1136
G. W. Kabalka et al. / Tetrahedron Letters 47 (2006) 1133–1136
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29.3, 22.6, 14.1. Calcd for C15H21F: C, 81.77; H, 9.61.
Found: C, 81.21; H, 9.94.
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