Microwave enhanced cross-coupling reactions involving potassium organotrifluoroborates

Article abstract of DOI:10.1016/j.tetlet.2005.07.036

Palladium catalyzed coupling reactions of potassium aryltrifluoroborates with aryl iodides occur rapidly utilizing microwave irradiation. The coupled products are produced in excellent yields.

Full text of DOI:10.1016/j.tetlet.2005.07.036

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6329–6331
Microwave enhanced cross-coupling reactions involving
potassium organotrifluoroborates
George W. Kabalka* and Mohammad Al-Masum
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 27 May 2005;revised 7 July 2005;accepted 8 July 2005
Abstract—Palladium catalyzed coupling reactions of potassium aryltrifluoroborates with aryl iodides occur rapidly utilizing micro-
wave irradiation. The coupled products are produced in excellent yields.
ꢀ 2005 Published by Elsevier Ltd.
The palladium catalyzed cross-coupling reaction
between organoboron compounds and organic halides
provides a powerful tool for the formation of carbon–
carbon bonds.1 Recently, the utility of potassium
organotrifluoroborates as intermediates for the synthesis
of biaryl compounds has become widely recognized.2,3
Both their straightforward preparation and chemical
reactivity add to the versatility of potassium organotri-
fluoroborates in organic synthesis. For example, reac-
tions of trifluoroborate reagents are unaffected by
water. They also proceed in a highly regio- and stereo-
selective manner. The reaction products are readily iso-
lated from the inorganic byproducts of the reaction.
BF3K
+
X
Pd
MW
R1
R1
R
R
1
3
2
Scheme 1.
Table 1. Microwave enhanced cross-coupling reactions of potassium
phenyltrifluoroborate with aryl iodides (Scheme 1)a
Entry Aryl iodide 2
Coupling product 3
Yieldsb
(%)
1
2
3
98
84
93
I
I
Cl
Cl
The use of microwaves in organic synthesis has also
gained importance.4 Microwave systems provide the
opportunity to complete complex reactions in minutes.
In this letter, we report the use of microwaves in
coupling reactions5 involving potassium organotrifluoro-
borates. We have found that palladium catalyzed cou-
pling reactions of potassium aryltrifluoroborates with
aryl iodides furnish the desired products within 10 min
in excellent yields whereas the same reactions require
several hours under thermal conditions (Scheme 1).
F
F
I
I
COCH3
COCH3
4
98
NO2
NO2
I
5
6
100
100
To evaluate the new procedure,6 potassium phenyltri-
fluoroborate was allowed to react with various substi-
tuted iodobenzenes (Table 1). A catalyst loading of
2 mol % PdCl2(dppf)CH2Cl2 with 3.0 equiv of HunigÕs
CH3O
I
CH3O
OCH3
CH3
OCH3
CH3
I
7
77
Keywords: Suzuki coupling;Trifluoroborates;Microwave;Organo-
boron.
CH3
CH3
a All reactions were run at 100 ꢁC for 10 min.
*
Corresponding author. Tel.: +1 865 974 3260;fax: +1 865 974
2997;e-mail: kabalka@utk.edu
b Isolated yields.
0040-4039/$ - see front matter ꢀ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.07.036

6330
G. W. Kabalka, M. Al-Masum / Tetrahedron Letters 46 (2005) 6329–6331
Table 2. Microwave enhanced cross-coupling reactions (Scheme 1)a
ArBF3K, 1
Aryl iodide, 2
Coupling product, 3
Yieldsb (%)
98
CF
3
BF K
3
CF
3
F
I
I
F
F
92
98
96
CH
3
F
CH3
BF3K
CF
3
BF K
3
I
I
Cl
CF3
F
Cl
BF3K
COCH3
COCH3
F
I
85
CH3
BF3K
CH3
CF3
I
86
94
CF3
BF3K
BF3K
CH
CH3
3
CF
3
I
CF3
CH O
3
CH O
3
F
F
BF K
3
50
I
F
F
F
F
F
F
i
a All reactions were run in PrOH–H2O (2:1) at 100 ꢁC for 10 min.
b Isolated yields.
base (i-Pr2NEt) in an isopropanol–water mixture (2:1)
was found to provide the coupled products in good to
excellent yields. In the absence of a palladium catalyst,
no coupling product was observed. The synthesis of
4-chlorobiphenyl is representative of the procedure
utilized (Table 1, entry 1). A dry Pyrex tube fitted with
an air-tight rubber cap was charged with potassium
phenyltrifluoroborate (92.0 mg, 0.50 mmol), 1-chloro-
4-iodobenzene (121.0 mg, 0.50 mmol), and PdCl2(dppf)-
CH2Cl2 (9.0 mg, 0.01 mmol). Under argon, HunigÕs base
(0.26 mL, 1.50 mmol) and argon-purged isopropanol–
water (2:1, 5.0 mL) were then added. The resulting mix-
ture was placed in a CEM microwave unit and allowed
to react at 100 ꢁC for 10 min. The reaction mixture was
transferred to a separatory funnel and diluted with ethyl
ether and water. The organic phase was separated and
dried over anhydrous sodium sulfate. The ether solution
was filtered and the filtrate concentrated prior to silica
gel chromatography using hexane–ethyl acetate (50:1).
The fractions were concentrated and dried in vacuo to
give 92.0 mg of pure 4-chlorobiphenyl (98%) as a white
solid. The reaction was insensitive to the nature of the
substituents on the aromatic ring. Reagents containing
electron withdrawing groups (Table 1, entries 1–4), elec-
tron donating groups (Table 1, entries 5 and 6) and ste-
rically bulky subtituents (Table 1, entry 7) all provided
coupling products in excellent yields. Having success-
fully demonstrated the use of microwaves to enhance
the Suzuki coupling of potassium phenyltrifluoroborate
with various aryl halides, we then investigated the use of
other substituted potassium aryltrifluoroborates in the
coupling reaction (Table 2). Essentially all reagents
provided the cross-coupling products in excellent yields.7
In conclusion, the microwave enhanced cross-coupling
reaction of potassium aryltrifluoroborates with substi-
tuted iodobenzenes provides an excellent route to highly
functionalized biaryl reagents.
Acknowledgements
We wish to thank the Department of Energy and the
Robert H. Cole Foundation for support of this research.
References and notes
1. (a) Miyaura, N.;Yamada, K.;Suzuki, A. Tetrahedron Lett.
1979, 36, 3437;(b) Miyaura, N.;Suzuki, A. Chem. Rev.
1995, 95, 2457;(c) Suzuki, A. In Metal-Catalyzed Cross-
Coupling Reactions;Diederich, F., Stang, P. J., Eds.;Wiley-
VCH: Weinheim, Germany, 1998, Chapter 2;(d) Suzuki, A.
J. Organomet. Chem. 1999, 576, 147;(e) Littke, A. F.;Fu,
G. C. Angew. Chem., Int. Ed. 2002, 41, 4176;(f) Barder, T.
E.;Walker, S. D.;Martinelli, J. R.;Buchwald, S. L. J. Am.
Chem. Soc. 2005, 127, 4685.
2. (a) Vedejs, E.;Chapman, R. W.;Fields, S. C.;Lin, S.;
Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020;(b) Darses,

G. W. Kabalka, M. Al-Masum / Tetrahedron Letters 46 (2005) 6329–6331
6331
S.;Michaud, G.;Genet, J.-P.
1875.
3. (a) Molander, G. A.;Rivero, M. R. Org. Lett. 2002, 4, 107;
(b) Molander, G. A.;Biolatto, B. J. Org. Chem. 2003, 68,
4302.
Eur. J. Org. Chem. 1999,
7.46 (m, 4H, –C6H4), 7.28–7.08 (m, 4H, –C6H4). 13C NMR
(CDCl3, 75.5 MHz): d 164.2, 160.9, 138.9, 128.7, 128.6,
128.4, 128.3, 121.2, 115.9, 115.6. 19F NMR (CDCl3,
282.3 MHz): d ꢀ58.2, ꢀ115.4. Calcd for C13H8OF4: C,
60.95;H, 3.15. Found: C, 61.52;H, 3.14. 4 0-Chloro-4-
trifluoromethoxy-biphenyl: 1H NMR (CDCl3, 300 MHz): d
7.55–7.26 (m, 8H, 2 · –C6H4); 19F NMR (CDCl3,
282.3 MHz): d ꢀ62.8. Calcd for C13H8OF3Cl: C, 57.27;
4. Lidstrom, P.;Tierney, J.;Wathey, B.;Westman, J.
Tetra-
hedron 2001, 57, 9925–9983.
5. For microwave assisted coupling reactions, see: (a)
Larhed, M.;Lindeberg, G.;Hallberg, A. Tetrahedron
0
H, 2.96. Found: C, 57.64;H, 2.91. 2-Methyl-4 -trifluoro-
Lett. 1996, 37, 8219;(b) Villemin, D.;Gomez-Escalo-
nilla, M. J.;Saint-Clair, J. F. Tetrahedron Lett. 2001, 42,
635;(c) Gong, Y.;He, W. Org. Lett. 2002, 4, 3803;(d)
Liu, Y.;Khemtong, C.;Hu, J.
398;(e) Wang, Y.;Sauer, D. R.
methoxy-biphenyl. 1H NMR (CDCl3, 300 MHz): d 7.34–
7.18 (m, 8H, 2 · –C6H4), 2.25 (s, 3H, –CH3). 19F NMR
(CDCl3, 282.3 MHz): d ꢀ58.1. Calcd for C14H11OF3: C,
0
Chem. Commun. 2004,
Org. Lett. 2004, 6,
66.67;H. 4.40. Found: C, 66.78;H, 4.44. 2-Methoxy-4
-
trifluoromethoxy-biphenyl. 1H NMR (CDCl3, 300 MHz): d
7.56–6.96 (m, 8H, 2 · –C6H4), 3.79 (s, 3H, –OCH3); 13C
NMR (CDCl3, 75.5 MHz): d 170.6, 156.3, 137.1, 130.8,
130.7, 129.1, 129.0, 120.8, 120.4, 111.1, 55.4; 19F NMR
(CDCl3, 282.3 MHz): d ꢀ58.0. Calcd for C14H11O2F3: C,
62.69;H, 4.13. Found: C, 62.64;H, 4.11. 2,4,6-4 0-Tetra-
fluoro-biphenyl: 1H NMR (CDCl3, 300 MHz): d 7.37 (m,
2H), 7.13 (m, 2H), 6.74 (m, 2H). 19F NMR (CDCl3,
282.3 MHz): d ꢀ109.1, ꢀ111.9, ꢀ113.5. Calcd for C12H6F4:
C, 63.73;H, 2.67. Found: C, 64.91;H, 2.80.
2793;(f) Solodenko, W.;Schoen, U.;Messinger, J.;
Glinschert, A.;Kirschning, A. Synlett 2004, 1699;(g)
Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250.
6. (a) Kabalka, G. W.;Dong, G.;Venkataiah, B. Org. Lett.
2003, 5, 3803;(b) Kabalka, G. W.;Mereddy, A. R.
Organometallics 2004, 23, 4519;(c) Solin, N.;Wallner, O.
A.;Szabo, K. J. Org. Lett. 2005, 7, 689.
7. Analytical data for new compounds: 40-Fluoro-4-trifluoro-
methoxy-biphenyl: 1H NMR (CDCl3, 300 MHz): d 7.53–