addition (8 h) of a solution of TTMSS (2 equiv), AIBN (2
equiv), and aryl halide 2 (1 equiv) in 5 mL of benzene, over
an additional 10 mL of benzene, 4a, at 80 °C (Entry 1,
Method A). The reaction did not go to completion when only
catalytic amounts of AIBN and TTMSS were employed
(Entry 2, Method B), even along with a stoichometric amount
of DABCO (Entry 3, Method C). Similar negative results
were obtained by replacing TTMSS with Bu3SnH (Entry 4,
Method D).18
4-methoxycarbonylphenyl bromides (2d-f, respectively)
(Entries 9-11) and obtained essentially the same results.
In conclusion, we report a simple method for the synthesis
of biaryl compounds, based on the intermolecular radical
addition of aryl- or heteroaryl radicals onto aromatic solvents.
This process takes place under reductive radical conditions
(TTMSS, AIBN), and it is noteworthy that radical addition
takes place prior to hydrogen abstraction from TTMSS. This
methodology should be complementary to the preparation
of biaryl compounds by organometallic-based aryl cross-
coupling methods and is currently being extended to the
synthesis of other related systems.
In a similar manner, 3-bromopyridine, 2b, and 4-bro-
mopyridine, 2c, reacted with benzene, 4a, to afford biaryl
derivatives 5b,c (Entries 5 and 6). Attempts to extend the
scope of the process were carried out using chlorobenzene,
4b, or toluene, 4c, as the aromatic solvents (Entries 7 and
8). The reactions took place smoothly to give an o:m:p
mixture of coupled products. The regioisomeric distribution
of the products on using chlorobenzene, 4b, as solvent differs
from that observed in other free-radical phenylations of aryl
compounds.19 In general, the regioselectivity depends on the
electrophilicity or nucleophilicity of both, the radical, and
the substrate as well as on polar effects and orbital control.
On the other hand, the philicity of aryl radicals is a
controversial subject and there has been considerable debate
regarding the nature of aryl radicals and whether they could
be nucleophilic,20 electrophilic,21,22 or relatively neutral7,23,24
species. Moreover, although chlorobenzene, 4b, could be
considered as an electron-poor substrate, the mesomeric
π-donor character of the Cl substituent must be taken into
consideration. In contrast, the isomeric distribution, o:m:p,
observed on using toluene, 4c, is in agreement with the
regioselectivity reported for other radical phenylations.19
On the assumption that aryl and heteroaryl radicals should
react in a similar manner, given that the unpaired electron
would be in an orbital orthogonal to the aromatic π-system
(π-excessive or π-deficient) and thus have little or no effect
on the reactivity of such species,25 we carried out additional
experiments using 4-methylphenyl, 4-methoxyphenyl, and
Acknowledgment. We thank Dr. J. Cristo´bal Lo´pez for
helpful discussions and Dr. Mijail Galajov for his assistance
in obtaining the NMR spectra. We acknowledge support of
this work from the Comisio´n Interministerial de Ciencia y
Tecnologia (CICYT) through the project PM97-0074 and the
Comunidad de Madrid (CAM) for a grant (A.G.V).
Supporting Information Available: Experimental pro-
cedures and spectral data for all compounds. This material
OL006722C
(17) Curran, D. P.; Yu, H.; Liu, H. Tetrahedron 1994, 50, 7343.
(18) The silane is a slightly less reactive hydrogen donor than the
stannane, presumably because the Si-H bond is 5 kcal M-1 stronger than
the corresponding Sn-H bond. On the other hand, the rate constants for
the reaction of an aryl radical with TTMSS is 3 times slower than stannane
and the aryl radical should add to an arene prior to reaction with the
hydrogen donor: Chatgilialoglu, C.; Dickhaut, J.; Giese, B. J. Org. Chem.
1991, 56, 6399. Kanabus-Kaminska, M.; Hawari, J. A.; Griller, D.;
Chatgilialoglu, C. J. Am. Chem. Soc. 1987, 109, 5267.
(19) (a) Fossey, J.; Lefor, D.; Sorba, J. Free Radicals in Organic
Chemistry; John Wiley and Sons: Masson, Paris, 1995; p 166. (b) Atkinson,
D. J.; Perkins M. J.; Ward, P. J. Chem. Soc. C 1971, 3240.
(20) Laird, E. R.; Jorgensen, W. L. J. Org. Chem. 1990, 55, 9.
(21) Ohkura, K.; Seki, K.; Terashima, M.; Kanaoka, Y. Tetrahedron Lett.
1989, 30, 3433.
(22) Vernin, G.; Jauffred, R.; Ricard, C.; Dou, H. J. M.; Metzger, J. J.
Chem. Soc., Perkin Trans. 2 1972, 1145.
(14) Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63, 2765.
(15) Crich, D.; Hwang, J.-T.; Gastaldi, S.; Recupero, F.; Wink, D. J. J.
Org. Chem. 1999, 64, 2877.
(23) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-
Carbon Bonds; Pergamon: New York, 1986; p 241.
(24) Curran, D. P. Synthesis 1988, 417.
(25) Jones, K.; Fiumana, A. Tetrahedron Lett. 1996, 37, 8049.
(16) Murphy, J. A.; Sherburn, M. S. Tetrahedron Lett. 1990, 31, 1625.
Org. Lett., Vol. 2, No. 24, 2000
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