ZnBr2-catalyzed efficient oxidative homo coupling of aryl magnesium bromides

Article abstract of DOI:10.1080/00397910600775499

Oxidative homo coupling of various arylmagnesium bromides in the presence of ZnBr₂ gave the corresponding symmetrical biaryls in moderate to good yields at room temperature. An efficient method under mild conditions without the use of reoxidant is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600775499

This article was downloaded by: [Brown University]
On: 26 August 2012, At: 03:01
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
ZnBr2‐Catalyzed Efficient Oxidative Homo
Coupling of Aryl Magnesium Bromides
S. Ravi Kanth a , G. Venkat Reddy a , T. Yakaiah a , B. Narsaiah a & P.
Shanthan Rao a
a Fluoroorganic Division, Indian Institute of Chemical Technology,
Hyderabad, India
Version of record first published: 16 Feb 2007
To cite this article: S. Ravi Kanth, G. Venkat Reddy, T. Yakaiah, B. Narsaiah & P. Shanthan Rao (2006):
ZnBr2‐Catalyzed Efficient Oxidative Homo Coupling of Aryl Magnesium Bromides , Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:20, 3079-3084
To link to this article: http://dx.doi.org/10.1080/00397910600775499
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

Synthetic Communicationsw, 36: 3079–3084, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600775499
ZnBr2-Catalyzed Efficient Oxidative
Homo Coupling of Aryl Magnesium Bromides
S. Ravi Kanth, G. Venkat Reddy, T. Yakaiah, B. Narsaiah,
and P. Shanthan Rao
Fluoroorganic Division, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: Oxidative homo coupling of various arylmagnesium bromides in the
presence of ZnBr2 gave the corresponding symmetrical biaryls in moderate to good
yields at room temperature. An efficient method under mild conditions without the
use of reoxidant is described.
Keywords: Aryl magnesium bromide, biaryls, homo coupling, zinc bromide
INTRODUCTION
Biaryls have gained importance in organic synthesis because of their versatile
applications in pharmaceuticals, polymers, and optically active ligands.[1] The
synthesis of biaryls via coupling reactions has been the subject of numerous
past and current investigations,[2] and these reactions are often prepared
from aryl halides by the classical Ullmann-type reaction.[3,4] Oxidative
homo coupling of aryl-metal reagents is one of the most efficient synthetic
methods for the construction of symmetrical biaryls[5] and is mainly based
on Co(II),[6] Cu(II),[7] Ti(IV),[8] TiCl,[9] or V(V)[10] as oxidants and
catalytic use of these metals in combination with reoxidants such as
molecular oxygen or dibromoethane.[11–13] In addition, recent research
interests have been limited to Pd- or Cu-catalyzed reactions of organo-
boron,[11] silicon,[12] and tin reagents.[13] Each method has its own
Received in India March 9, 2006
IICT Communication No. 050507
Address correspondence to B. Narsaiah, Fluoroorganic Division, Indian Institute of
Chemical Technology, Hyderabad 500 007, India. E-mail: narsaiah@iict.res.in
3079

3080
S. R. Kanth et al.
drawbacks in terms of conversion, selectivity, and isolation procedures.
Therefore, development of an efficient and economically viable method for
the synthesis of symmetrical biaryls is of interest.
RESULTS AND DISCUSSION
In continuation of our efforts,[14,15] we have developed a feasible method of
synthesis for symmetrical biaryls and studied various oxidants such as
ZnCl2, Zn(OAc)2, and ZnBr2 independently as catalysts and in combination
with reoxidants such as dibromoethane for oxidative homocoupling of aryl
magnesium bromides. Results of the oxidative homo coupling reaction of
phenyl magnesium bromide with different catalysts with and without reoxi-
dants to obtain biaryls are summarized in Table 1.
ZnBr2 is an efficient catalyst in the absence of reoxidant for the homo
coupling reaction. ZnBr2 undergoes reduction followed by oxidation to
catalyze the reaction. It is known[6,16] that the metal halides on reaction
with aryl magnesium bromides undergo reduction to a lower oxidation state
and subsequently oxidize in a chain reaction. Thus, in general metal halides
are claimed as oxidation–reduction catalysts and provide oxidative homo
coupling of aryl magnesium bromides to form biaryls. The mechanism of
reaction is formulated below in cyclic form (Scheme 1).
The reaction is further studied with various aryl magnesium bromides to
see the versatility of the reaction. Substituents such as electron donors or
electron acceptors on the phenyl ring had no influence on the rate of
reaction and yield of products. However, sterically hindered or ortho-substi-
tuted aryl magnesium bromides had longer reaction times and gave the corre-
sponding biaryls in moderate to good yields. Reactions were carried out in
diethylether or tetrahydrofuran (THF) at room temperature under mild con-
ditions with neat workup procedure. In a typical reaction, aryl magnesium
bromide is prepared using aryl bromide and magnesium metal in diethyl
ether/THF, and the generated aryl magnesium bromide in situ is catalyzed
with 5 mol% ZnBr2. Biaryls are obtained with a yield as high as 98%. The
Table 1. Studies on roles of various oxidants
Entry
Catalyst
Reoxidant
Time (h)
Yield (%)
1
2
3
4
5
6
ZnBr2
ZnBr2
1,2-Dibromethane
—
1,2-Dibromethane
1
1
6
6
2
2
80
98
—
—
55
70
Zn(OAc)2
Zn(OAc)2
ZnCl2
—
1,2-Dibromethane
—
ZnCl2

Homo Coupling of Aryl Magnesium Bromides
3081
Scheme 1.
sequence of reaction is drawn in Scheme 2, and results are summarized in
Table 2.
CONCLUSION
In conclusion, we have found that the ZnBr2-induced homo coupling reaction
of aryl magnesium bromides proceeds efficiently in ether/THF under mild
conditions at room temperature. This procedure is applicable to a variety of
substituted aryl magnesium bromides.
EXPERIMENTAL
General Procedure for ZnBr2-Catalyzed Homo Coupling Reaction
of Aryl Magnesium Bromides
Magnesium turnings (2.5 mmol) and diethyl ether (3 mL) were placed in a
flask under an N2 atmosphere; substituted bromo benzene (2.9 mmol) in
Scheme 2.

3082
S. R. Kanth et al.
Table 2. Preparation of symmetrical biaryls by oxidative homocoupling reaction
Time
(h)
Yield
(%)a
Entry
1
Substrate
Product
1
2
4
98
2
3
94
80
4
5
2
3
95
78
6
6
68
7
3
5
88
80
8b
9b
4
2
85
10
82
(continued)

Homo Coupling of Aryl Magnesium Bromides
3083
Table 2. Continued
Time
(h)
Yield
(%)a
Entry
11b
Substrate
Product
4
87
12
13
2
2
92
90
aYields of isolated products.
bReactions were carried out in THF.
diethyl ether (3 mL) was slowly added over a period of 30 min at 0–108C and
stirred for 0.5 h at room temperature. The Grignard reagent thus formed was
added to a mixture of 5 mol% ZnBr2 (0.125 mmol) in diethyl ether (5 mL) and
stirred for 1–6 h at room temperature. The progress of the reaction was
monitored by TLC at regular intervals. The reaction mixture was diluted
with water and extracted with ethyl acetate (2 Â 10 mL). The ethyl acetate
extract was dried over sodium sulphate and concentrated in vacuo. Purification
was carried out by column chromatography using 60 to 120-mesh silica-gel
and gave the corresponding biphenyl.
ACKNOWLEDGMENTS
Authors thank J. S. Yadav, director, IICT, Hyderabad, and Shri S. Narayan
Reddy, head, Fluoroorganic Division, IICT, for their constant encouragement.
S. R. K. is grateful to Council of Scientific and Industrial Research (CSIR),
New Delhi, for the grant of a senior research fellowship.
REFERENCES
1. Rosini, C.; Franzini, L.; Raffael, A.; Dalvadori, P. Synthesis 1992, 503.
2. Knight, D. W. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
(Eds.); Pergamon: Oxford, 1991; Vol. 3, p. 499, Chapter 2.3.

3084
S. R. Kanth et al.
3. (a) Fanta, P. E. Chem. Rev. 1946, 38, 139; (b) Fanta, P. E. Chem. Rev. 1964, 64,
613; (c) Fanta, P. E. Synthesis 1974, 9.
4. For recent examples of nickel- or palladium-catalyzed reactions, see
(a) Yamamoto, T.; Wakabayashi, S.; Osakada, K. J. Organometet Chem. 1992,
428, 223; (b) Venkatraman, S.; Li, C. J. Tetrahedron Lett. 2000, 41, 4831;
(c) Alonso, D. A.; Najera, C.; Pacheco, M. C. Org. Lett. 2000, 2, 1823;
(d) Hennings, D. D.; Iwama, T.; Rawal, H. Org. Lett. 1999, 1, 1205;
(e) Venkatraman, S.; Li, C. J. Org. Lett. 1999, 1, 1133.
5. (a) March, J. Advanced Organic Chemistry, 4th ed.; March, J. (Ed.); Wiley:
New York, 1992; 725–726; (b) Kauffmann, T. Angew. Chem., Int. Ed. Engl.
1974, 13, 219; (c) Hassan, J.; Sevignon, M.; Gzzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 13509.
6. Kharasch, M. S.; Fields, E. K. J. Am. Chem. Soc. 1941, 63, 2316.
7. Sakellarious, E.; Kyrimis, T. Ber. Dtsch. Chem. Ges. 1924, 57B, 322.
8. Inoue, A.; Kitagawa, K.; Shinokubo, H.; Oshima, K. Tetrahedron 2000, 56, 9601.
9. McKillop, A.; Elsom, L. F.; Taylor, E. C. J. Am. Chem. Soc. 1968, 90, 2423.
10. For recent reports of oxidative coupling by oxovanadium species, see
(a) Ishikawa, T.; Ogawa, A.; Hirao, T. J. Am. Chem. Soc. 1998, 120, 5124;
(b) Hirao, T.; Takada, T.; Ogawa, A. J. Org. Chem. 2000, 65, 1511.
11. (a) Rao, V. V. R.; Kumar, C. V.; Devaprabakara, D. J. Organomet. Chem. 1979,
179, C7; (b) Song, Z. Z.; Wong, H. N. C. J. Org. Chem. 1994, 59, 33;
(c) Moreno-Manas, M.; Perez, M.; Pleixats, R. J.Org.Chem. 1996, 61, 2346;
(d) Smith, K. A.; Campi, E. M.; Jackson, W. R.; Marcuccio, S.; Naeslund, C. G.
M.; Deacon, G. B. Synlett 1997, 131; (e) Koza, D. J.; Carita, E. Synthesis 2002,
2183; (f) Kabalka, G. W.; Wang, L. Tetrahedron Lett. 2002, 43, 3067;
(g) Klingensmith, L. M.; Leadbeater, N. E. Tetrahedron Lett. 2003, 44, 765;
(h) Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai, A. Tetrahedron Lett. 2003,
44, 1541; (i) Punna, S.; Diaz, D. D.; Finn, M. G. Synlett 2004, 2351.
12. (a) Kang, S. K.; Kim, T. H.; Pyun, S. J. J. Chem. Soc., Perkin Trans. 1 1997, 797;
(b) Yamaguchi, S.; Ohno, S.; Tamao, K. Synlett 1997, 1199.
13. (a) Kanemoto, S.; Matsubara, S.; Oshima, K.; Utimoto, K.; Nozaki, H. Chem. Lett.
1987, 5; (b) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J. Org. Chem.
1993, 58, 5434; (c) Shirakawa, E.; Nakao, Y.; Murota, Y.; Hiyama, T.
J. Organomet. Chem. 2003, 670, 132.
14. Rama Rao, V. V. V. N. S.; Venkat Reddy, G.; Maitraie, D.; Ravikanth, S.;
Yadla, R.; Narsaiah, B.; Shanthan Rao, P. Tetrahedron 2004, 60, 12331.
15. Maitraie, D.; Venkat Reddy, G.; Rama Rao, V. V. V. N. S.; Ravikanth, S.;
Narsaiah, B.; Shanthan Rao, P.; Ravikumar, K.; Sridhar, B. Tetrahedron 2005,
61, 3999.
16. Nagano, T.; Hayashi, T. Org. Lett. 2005, 7, 491.