Pd(II)-catalyzed synthesis of unsymmetrical biaryls from tetraphenylborate and aryl halides under microwave activation

Article abstract of DOI:10.1081/SCC-120037920

A rapid and efficient method for synthesis of unsymmetrical biaryls under microwave irradiation conditions is described. The process involves the reactions of sodium tetraphenylborate with aryl halides in the presence of catalytic amount [PdCl₂(PPh₃)₂] with KF/Al ₂O₃ under microwave irradiation to afford the unsymmetrical biaryls in good to excellent isolated yields.

Full text of DOI:10.1081/SCC-120037920

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 11, pp. 2063–2069, 2004
Pd(II)-Catalyzed Synthesis of
Unsymmetrical Biaryls from
Tetraphenylborate and Aryl Halides
Under Microwave Activation
*
Jin-Xian Wang, Yihua Yang, and Bangguo Wei
Department of Chemistry, Institute of Chemistry, Northwest Normal
University, Lanzhou, P.R. China
ABSTRACT
A rapid and efficient method for synthesis of unsymmetrical biaryls under
microwave irradiation conditions is described. The process involves
the reactions of sodium tetraphenylborate with aryl halides in the
presence of catalytic amount [PdCl2(PPh3)2] with KF/Al2O3 under
microwave irradiation to afford the unsymmetrical biaryls in good to
excellent isolated yields.
Key Words: Palladium-catalyzed; Suzuki reaction; Microwave irradia-
tion; Cross-coupling reactions.
*
Correspondence: Jin-Xian Wang, Department of Chemistry, Institute of Chemistry,
Northwest Normal University, 805 An Ning Road (E.), Lanzhou 730070, P.R. China;
E-mail: wangjx@nwnu.edu.cn.
2063
DOI: 10.1081/SCC-120037920
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
2064
Wang, Yang, and Wei
INTRODUCTION
The palladium-catalyzed Suzuki cross-coupling[1] reaction of organo-
borate compounds with organic electrophiles is one of the most-efficient
methods for the construction of carbon–carbon bonds. Indeed, in recent years,
various efficient Pd catalyst precursors have been developed that allow aryl
iodides, bromides, triflates, and chlorides to be effectively coupled with aryl
boronic acids under mild reaction conditions.[2–4] Recently, Bumagin[2a]
reported that the cross-coupling reaction of NaBPh4 with acyl chlorides in
the presence of Pd(OAc)2 and Na2CO3 in dry or aqueous acetone gives high
yields of unsymmetric ketones.
Microwave irradiation is known to accelerate many organic reactions in
polar solvents or in the absence of solvent, and some important reviews on
its application have been published.[5] Recently, we have reported the synth-
esis of unsymmetrical ketones[6] and conjugated acetylenic ketones[7] cata-
lyzed by palladium(II) complex or copper(I) under microwave irradiation
conditions. Several microwave assisted palladium-catalyzed cross-coupling
reactions have been reported.[8]
In this paper, we wish to report a very simple, fast, economically viable
and general method for palladium-catalyzed cross-coupling reactions of
sodium tetraphenylborate with aryl halides in the presence of KF/Al2O3
under microwave irradiation conditions. The reactions are shown in Sch. 1,
and results are summarized in Table 1. The results in Table 1 showed that
the activities of aryl halides are in the following order: iodides . bromides .
chlorides.
Using the reaction of sodium tetraphenylborate with bromobenzene as an
example, we investigated the effects of the power and time of microwave
irradiation for the formation of 3a. The results are summarized in Tables 2
and 3. It was found that the high yield unsymmetric biaryls could be obtained
at 675 W for 10 min under microwave irradiation conditions.
The amount of [PdCl2(PPh3)2] affected the yield, and the use of 5 mol% of
the catalyst gives the best result. We investigated the effect of bases on the
reaction of sodium tetraphenylborate with bromobenzene. It was found
that the activity of bases is in the following sequence: KF/Al2O3 . NaOH/
Al2O3 . KF . Na3PO4/Al2O3 . Na2CO3/Al2O3 . Al2O3.
Scheme 1.

ORDER
REPRINTS
Pd(II)-Catalyzed Synthesis of Unsymmetrical Biaryls
2065
Table 1. Preparation of unsymmetric biaryls 3a–j.
Entrya
R (Ar)
X
Productb
Yield (%)c
1
2
Ph
Ph
Ph
I
3a
3a
3a
3b
3c
3d
3e
3f
97
88
78
82
84d
86
80
90
92
87
88
89
79
Br
Cl
Br
Br
Br
Br
I
3
4
4-CH3C6H4
4-BrC6H4
2-C10H7
5
6
7
1-C10H7
8
3-CH3C6H4
4-O2NC6H4
4-O2NC6H4
2-O2NC6H4
4-CH3OC6H4
2,5-Dimethylphenyl
9
I
3g
3g
3h
3i
10
11
12
13
Cl
I
I
Br
3j
aMole ratio: NaBPh4 : aryl halide : [PdCl2(PPh3)2] : KF/Al2O3 ¼ 1 : 1.7 : 0.05 : 3.2.
1
bAll products were determined by IR, H NMR, and MS.
cIsolated yield.
dThe product is 4-biphenylyl benzene.
The effectiveness of the microwave irradiation and conventional heating
for the formation of compounds 3a–j has been compared, and the results
showed that the synthesis of compounds 3a–j under microwave irradiation
were 144 times faster than under conventional heating. This ratio between
the reaction time using conventional reflux and microwave irradiation (tc/
t
mw) under same condition, quantifies the microwave heating effect.
EXPERIMENTAL
Microwave irradiation was carried out with a commercial microwave
oven Glanz WP 750B at 2450 Hz. 1H NMR spectra were recorded at
Table 2. Effect of the power of microwave irradiation on the formation of 3a.a
Power (W)
Yield (%)b
375
31
450
46
525
57
600
69
675
88
750
83
aThe reaction was carried out in the presence of KF/Al2O3 using [PdCl2(PPh3)2]
as catalyst in DMF under nitrogen. Mole ratio: NaBPh4 : bromobenzene :
[PdCl2(PPh3)2] ¼ 1 : 1.4 : 0.05.
bIsolated yield.

ORDER
REPRINTS
2066
Wang, Yang, and Wei
Table 3. Effect of the time of microwave irradiation on the formation of 3a.a
Time (min)
Yield (%)b
3
33
5
48
7
65
8
80
9
84
10
88
11
88
11
50c
13
88
aThe reaction was carried out in the presence of KF/Al2O3 using [PdCl2(PPh3)2] as
catalyst in DMF under nitrogen. Mole ratio: NaBPh4 : bromobenzene : [PdCl2
(PPh3)2] ¼ 1 : 1.4 : 0.05.
bIsolated yield.
cNone supported reagents (KF/Al2O3).
200 MHz on a Bruker PT 200A spectrometer in CDCl3 with tetramethylsilane as
internal standard. Chemical shifts were reported as d in ppm. IR spectra were
measured with an Alpha Centauri FI-IR spectrometer as KBr discs. Mass spec-
tra were recorded on a QP-1000A GC-MS using the electron ionization mode
(70eV). Melting points were determined with an electrothermal micromelting
point apparatus and are uncorrected. All solvents were used without further
purification. The [PdCl2(PPh3)2] was prepared according to Ref.[9]
General Procedure for the Preparation of Compounds 3a–j
A mixture of sodium tetraphenylborate (1 mmol), aryl halide (1.7 mmol),
[PdCl2(PPh3)2] (0.05 mmol), KF/Al2O3 (3.2 mmol), and DMF (15 mL) was
irradiated at 675 W for 10 min by microwaves under a nitrogen atmosphere.
The precipitate was filtrated, and the filtrate was poured into a saturated aqueous
sodium chloride (50 mL) and extracted with diethyl ether (3 ꢀ 20 mL).
The extracts were washed with water (3 ꢀ 20 mL) and then dried over with
magnesium sulfate. The dried diethyl ether solution was concentrated to
yield crude product, which was purified by column chromatography on silica
gel (200–300 mesh) using petroleum/ethyl acetate (v/v, 20 : 1) as eluant or
recrystallized 3a–j in 78–90% yield. The following compounds were
obtained:
Biphenyl (3a). M.p.: 68–698C (Lit.[10]: 708C). IR (KBr): 13,033, 1943,
1597, 1569, 1479, 1429, 1344, 1170, 1006, 983, 729, 696. 1H NMR (200 MHz,
CDCl3): 7.67–7.25 (m, 10H). EI-MS (m/z, %): 154 (Mþ, 100).
4-Methylbiphenyl (3b). M.p.: 44–468C (Lit.[11]: 47.58C). IR (KBr):
3038, 2932, 2876, 1608, 1568, 1516, 1486, 1444, 1403, 1376, 1129, 1006,
1
910, 822, 755, 609. H NMR (200 MHz, CDCl3): 7.60–7.22 (m, 9H), 2.39
(s, 3H). EI-MS (m/z %): 168 (Mþ), 77 (100%).
4-Bromobiphenyl (3c). M.p.: 212–2138C (Lit.[12]: 208–2108C). IR
(KBr): 3033, 1595, 1576, 1480, 1454, 1404, 1160, 910, 839, 746, 600. H
1

ORDER
REPRINTS
Pd(II)-Catalyzed Synthesis of Unsymmetrical Biaryls
2067
NMR (200 MHz, CDCl3): 7.69–7.37 (m, 14H); EI-MS (m/z, %): 220 (Mþ),
77 (100).
2-Phenylnaphthalene (3d). M.p.: 97–988C (Lit.[13]: 95–968C); IR
(KBr): 13,053, 1947, 1597, 1494, 1453, 1361, 1130, 893, 860, 821, 771,
1
680. H NMR (200 MHz, CDCl3): 8.07–7.25 (m, 12H). EI-MS (m/z, %):
204 (Mþ, 100).
1-Phenylnaphthalene (3e). Oil: (Lit.[14]: 191–1998C/5 mmHg). IR
(neat): 3056, 1592, 1597, 1494, 1395, 802, 779, 761, 617. 1H NMR
(200 MHz, CDCl3): 7.91–7.76 (m, 3H), 7.48–7.30 (m, 9H). EI-MS (m/z,
%): 204 (Mþ, 100).
3-Methylbiphenyl (3f). M.p.: 42–438C (Lit.[15]: 110–1158C/2 mmHg).
IR (KBr): 3032, 1980, 1600, 1567, 1520, 1486, 1406, 1377, 1129, 1026, 1006,
823, 756, 609. 1H NMR (200 MHz, CDCl3): 8.58–7.20 (m, 9H), 2.37 (s, 3H);
EI-MS (m/z, %): 168 (Mþ, 100).
4-Nitrobiphenyl (3g). M.p.: 112–1138C (Lit.[16]: 1138C). IR (KBr):
1
1576, 1513, 1345, 1206, 1006, 853, 748, 693; H NMR (200 MHz, CDCl3):
8.32–8.28 (m, 2H), 7.75–7.25 (m, 7H). EI-MS (m/z, %): 199 (Mþ, 100).
2-Nitrobiphenyl (3h). Oil: (Lit.:[15] 142–1478C/2 mmHg). IR (neat):
3063, 1601, 1570, 1525, 1354, 1076, 853, 783, 740, 699. 1H NMR
(200 MHz, CDCl3): 7.77–7.14 (m, 9H). EI-MS (m/z, %): 199 (Mþ, 100).
4-Methoxybiphenyl (3i). M.p.: 88–898C (Lit.[17]: 90–918C). IR (KBr):
1
3034, 2908, 2843, 1604, 1592, 1486, 1437, 1343, 1138, 918, 823, 756. H
NMR (200 MHz, CDCl3): 7.55–6.96 (m, 9H), 3.86 (s, 3H). EI-MS (m/z,
%): 184 (Mþ, 100).
2,5-Dimethylbiphenyl (3j). Oil: (Lit.[18]: 107–1098C/2 mmHg). IR
(KBr): 3036, 2960, 2820, 1600, 1550, 1520, 1486, 1440, 1380, 1123, 1015,
1
890, 810, 760, 600. H NMR (200 MHz, CDCl3): 7.43–7.16 (m, 8H), 2.43
(s, 3H), 2.08 (s, 3H). EI-MS (m/z, %): 182 (Mþ, 100).
ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of
China (No. 20272047) and the Gansu Key Discipline Foundation of China.
REFERENCES
1. (a) Zhang, F.-J.; Cortez, C.; Harvey, R.G. New synthetic approaches to poly-
cylic aromatic hydrocarbons and their carcinogenic oxidized metabolites:
derivatives of benzo[rst] pentaphene and dibenzo[b,def]chrysene. J. Org.
Chem. 2000, 65, 3952–3960; (b) Kabalka, G.W.; Pagni, R.M.; Hair, C.M.

ORDER
REPRINTS
2068
Wang, Yang, and Wei
Solventless suzuki coupling reactions on palladium-doped KF/Al2O3. Org.
Lett. 1999, 1, 1423–1425; (c) Varma, R.S.; Naicker, K.P. Palladium chlor-
ide/tetraphenylphosphonium bromide intercalated clay: new catalyst for
cross-coupling of aryl halides with arylboronic acids. Tetrahedron Lett.
1999, 40, 439–442; (d) Miyaura, N.; Suzuki, A. Palladium-catalyzed
cross-coupling reactions of organoboron compounds. Chem. Rev. 1995,
95, 2457–2483; (e) Kang, S.-K.; Lee, H.-W.; Jang, S.-B.; Ho, P.-S.
Palladium-catalyzed cross-coupling of organoboron compounds with
iodonium salts and iodanes. J. Org. Chem. 1996, 61, 4720–4724.
2. (a) Bumagin, N.A.; Korolev, D.N. Synthesis of unsymmetric ketones via
ligandless Pd-catalyzed reaction of acyl chlorides with organoboranes.
Tetrahedron Lett. 1999, 40, 3057–3060; (b) Cai, M.-Z.; Song, C.-S.;
Huang, X. Silica-supported phosphine palladium(0) complex catalyzed
phenylation of acid chlorides and aryl iodides by sodium tetraphenyl-
borate. Synth. Commun. 1998, 28, 693–700; (c) Cho, C.S.; Itotani, K.;
Uemura, S. Sodium tetraphenylborate as a phenylating reagent in the
palladium-catalyzed phenylation of alkenes and acid chlorides.
J. Organomet. Chem. 1993, 443, 253–259.
3. Miyaura, A.; Yanagi, T.; Suzuki, A. The palladium-catalyzed cross-
coupling reaction of phenylboronic acid with haloarenes in the presence
of bases. Synth. Commun. 1981, 11, 513–519.
4. Nielsen, S.F.; Peters, D.; Axelsson, O. The suzuki reaction under solvent-
free conditions. Synth. Commun. 2000, 30, 3501–3509.
5. (a) Varma, R.S. Solvent-free organic syntheses. Green Chem. 1999, 1,
43–55; (b) Loupy, A.; Petit, A.; Hamelin, J.; Boullet, F.T.;
Jacquault, P.; Mathe, D. New solvent-free organic synthesis using focused
microwaves. Synthesis 1998, 1213–1234.
6. (a) Wang, J.-X.; Yang, Y.H.; Wei, B.G.; Hu, Y.L.; Fu, Y. Microwave-
assisted cross-coupling reaction of sodium tetraphenylborate with aroyl
chlorides on palladium-doped KF/Al2O3. Bull. Chem. Soc. Jpn. 2002,
75, 1381–1382; (b) Wang, J.-X.; Wei, B.G.; Hu, Y.L.; Liu, Z.X.;
Yang, Y.H. Microwave promoted palladium-catalyzed phenylation of
aroyl chlorides and sodium tetraphenylborate. Synth. Commun. 2001,
31, 3885–3890.
7. Wang, J.-X.; Wei, B.G.; Hu, Y.L.; Liu, Z.X.; Fu, Y. Microwave-assisted
coupling reaction by copper(I)-catalyzed of terminal alkynes with aroyl
chlorides. Synth. Commun. 2001, 31, 3527–3532.
8. (a) Larhed, M.; Lindeberg, G.; Hallberg, A. Rapid microwave-assisted
Suzuki coupling on solid-phase. Tetrahedron Lett. 1996, 37,
8219–8222; (b) Larhed, M.; Hallberg, A. Microwave-promoted
palladium-catalyzed coupling reactions. J. Org. Chem. 1996, 61,
9582–9584; (c) Blettner, C.G.; Konig, W.A.; Stenzel, W.; Schotten, T.

ORDER
REPRINTS
Pd(II)-Catalyzed Synthesis of Unsymmetrical Biaryls
2069
Microwave-assisted aqueous Suzuki cross-coupling reactions. J. Org.
Chem. 1999, 64, 3885–3890; (d) Wang, J.-X.; Liu, Z.X.; Hu, Y.L.;
Wei, B.G.; Bai, L. Microwave-promoted palladium catalysed Heck
cross coupling reaction in water. J. Chem. Res. (s) 2000, 484–485.
9. Itatani, H.; Bailar, J.C. Homogenous catalysis in the reactions of olefinic
substances. V. Hydrogenation of soybean oil methyl ester with triphenyl-
phosphine and triphenylarsine palladium catalysts. J. Am. Oil Chem. Soc.
1967, 44, 147–151.
10. Forrest, J. The Ullmann biaryl synthesis. Part II. The effect of m-dinitrated
diluents on the self-condensation of iodobenzene. J. Chem. Soc. 1960,
574–580.
11. Sherwood, I.R.; Short, W.F.; Stansfieled, R. The preparation of unsym-
metrical diphenyl derivatives. J. Chem. Soc. 1932, 1832–1835.
12. Gary, W.M.; Beverly, S. Syntheses of para-terphenyl via reductive deoxy-
genation of quinol derivatives. Synth. Commun. 1995, 25, 269–276.
13. Tius, M.A. Aromatic annelation: application to the synthesis of unsym-
metrical biphenyls. Tetrahedron Lett. 1981, 22, 3335–3338.
14. Mowery, M.E.; Deshong, P. Synthesis of unsymmetrical biaryls by
palladium-catalyzed cross coupling reactions of arenas with tetrabutyl-
ammonium triphenyldifluorosilicate. A hypervalent silicon reagent.
J. Org. Chem. 1999, 64, 3266–3270.
15. Oae, S.; Shinhama, K.; Kim, Y.H. Direct conversion of arylamines to the
corresponding halides, biphenyls, and sulfides with t-butyl thionitrate.
Bull. Chem. Soc. Jpn. 1980, 53, 2023–2026.
16. Ahmad, Y.; Qureshi, M.I.; Baig, M.I. Studies of the acylarylnitrosamine
reaction. I. The use of nitrosylsulfuric acid in the preparation of unsym-
metrical biaryls. Can. J. Chem. 1967, 45, 1539–1542.
17. Tamura, Y.; Chun, M.-W.; Inoue, K.; Minamikawa, J. A novel synthesis
of biaryls from diaryliodonium salts. Synthesis 1978, 822.
18. Weisburger, E.K.; Weisburger, J.H. A new route to 3- and 2, 6-substituted
fluorenes. J. Org. Chem. 1958, 23, 1193–1198.
Received in Poland September 30, 2003

Copyright of Synthetic Communications is the property of Taylor & Francis Ltd and its content may not be
copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.