LETTER
The MoCl5-Mediated Oxidative Aryl-aryl Coupling
623
As anticipated the more electron rich substrates give sig-
nificantly higher yields (Scheme 3, Table 2). The forma-
tion of 2,2 ,4,4 ,5,5 -hexamethoxybiphenyl 13 was almost
quantitative. The conversion of the phenyl ether analogue
8 was accompanied with traces of dibenzofurans, which
were easily removed. If strong electron withdrawing
groups were involved, no conversion occurred. The alde-
hyde moiety remained unchanged and the starting materi-
al was recovered. Using weaker electron withdrawing
groups, like halogens, also gave access to the biphenyl
systems incorporating fluoro or bromo substituents. No
exchange of the substituents by molybdenum pentachlo-
ride was observed. In all cases no chlorinated by-products
of the oxidative C–C coupling were detected.
OCH3
hexamethoxytriphenylene
OCH3
3
OCH3
OCH3
4
OCH3
H3CO
5
Scheme 2 Reagents and conditions: 2 equiv MoCl5, CH2Cl2, r.t., 1
h; standard for GC-control: n-hexadecane.
In conclusion, the MoCl5-mediated oxidative coupling of
dialkoxy-substituted benzenes requires approximately
two equivalents of molybdenum pentachloride for each
C–C bond formation. For a successful performance a 1,2-
dialkoxy-substitution pattern is pivotal. When employing
4-substituted veratrole derivatives as substrates 3,3 ,4,4 -
tetramethoxybiphenyls result in good yields. A variety of
substituents are tolerated. The application to the total syn-
thesis of natural products will be reported in due course.
ond proton. During this rapid conversion the evolution of
HCl can be observed. At least under ambient temperature
the described innersphere radical transfer can be anticipat-
ed. When molybdenum pentachloride is applied under
harsher conditions an unselective reaction pattern will
take place, forming several oxidative coupling and chlori-
nating products.
Acknowledgement
Since the construction of the 3,3 ,4,4 -tetramethoxybi-
phenyl moiety is of important significance for the synthe-
This work was supported by the Fonds der Chemischen Industrie
sis of naturally occurring lignans,9 we focussed on the and the Deutschen Forschungsgemeinschaft (DFG). The gift of
MoCl5 by H. C. Starck (Goslar, Germany) was very helpful.
oxidative coupling of substituted 1,2-dimethoxy benzenes
having substituents in the 4-position to prevent the tri-
phenylene formation. Best results also were obtained
when employing two equivalents of molybdenum pen-
tachloride for each C–C coupling.
References
(1) (a) Hirao, T.; Kohno, S.; Oshiro, Y.; Agawa, T. Bull. Chem.
Soc. Jpn. 1983, 56, 1569. (b) Hirao, T.; Kohno, S.; Enda, J.;
Ohshiro, Y.; Agawa, T. Tetrahedron Lett. 1981, 22, 3633.
(c) McCann, E. L. III.; Brown, T. M. Inorg. Synth. 1970, 12,
181. (d) Filippo, J. S. Jr.; Sowinski, A. F.; Romano, L. J. J.
Am. Chem. Soc. 1975, 97, 1599.
R
OCH3
OCH3
H3CO
H3CO
H3CO
H3CO
R
(2) Kumar, S.; Manickam, M. Chem. Commun. 1997, 1615.
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(4) All reactions were strictly performed under inert atmosphere
using anhydrous solvents. Different grades of molybdenum
pentachloride from various suppliers were tested having
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R
12-17
6-11
Scheme 3 Reagents and conditions: MoCl5, CH2Cl2, r.t., 30 min.
Table 2 Oxidative Coupling of Veratrole Derivatives 6–11
Entry Reactant
R
Product Yield (%)b mp (°C)
1
2
3
4
5
6
6
CH3
OCH3
OPh
CHO
F
12
67
98
71
119 (11811)
178 (19012)
126
7
13
810
9
1413
15
0 (93)c
–
(8) (a) Yasui, S.; Tsujimoto, M.; Itoh, K.; Ohno, A. J. Org.
Chem. 2000, 65, 4715. (b) Rathore, R.; Bosch, E.; Kochi, J.
K. Tetrahedron 1994, 50, 6727.
(9) (a) Ward, R. S.; Hughes, D. D. Tetrahedron 2001, 57, 5633.
(b) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 977.
10
11
1614
17
58
63
143
Br
159 (15915)
a All reactions were performed on a 4 mmol scale.
b Yields refer to isolated products after column chromatography on
(10) Synthesis of 8: Janssen, D. E.; VanAllan, J.; Wilson, C. V. J.
Org. Chem. 1955, 20, 1326.
silica.
c Re-isolated starting material.
Synlett 2002, No. 4, 622–624 ISSN 0936-5214 © Thieme Stuttgart · New York