aryl siloxane, 2 equiv of catechol, and triethylamine. This
report details the successful application of microwave
irradiation to the coupling of aryl bis(catechol) silicates with
aryl bromides.
Table 1. Probing the Functional Group Tolerance of the
Microwave Assisted Coupling Reaction
The coupling of silicate 2 with bromobenzene under
idealized thermal conditions had resulted in the formation
of biphenyl in a yield of only 38%.4e However, under the
influence of microwave irradiation, rapid and efficient cross-
coupling of aryl bromides was realized (Scheme 2).
entry
R
yield (%)
1
2
3
4
5
6
7
8
9
10
H
89
81
84
88
86
80
84
89
93
0
Scheme 2
4-OCH3
2-OCH3
4-t-Bu
2-CH3
2,6-dimethyl
1-naphthyl
4-COCH3
4-NO2
4-NH4
thermal conditions had also failed in the presence of free
amino groups.4e
Reaction conditions for this coupling are analogous to
the thermal reaction and entailed 5 mol % Pd(dba)2 as the
Pd(0) source, 5 mol % dicyclohexyl phosphinobiphenyl (3),
and 1.5 equiv of tetrabutylammonium fluoride (TBAF) in
THF (Scheme 2). Exposure of the reaction mixture to
microwave irradiation (50 W/10 min/120 °C) led to efficient
cross-coupling of bromobenzene with triethylammonium
phenyl bis(catechol) silicate (2). In the absence of irradiation,
the yield of coupling product under identical conditions was
<40%.4e
Once the feasibility of the coupling of simple aryl
bromides had been demonstrated, attention turned to the
cross-coupling of more complex substrates bearing multiple
functional groups. In the less idealized world of natural
product synthesis, one can determine the full scope of the
new coupling protocol only by investigating these more
complex substrates. The results of these investigations are
shown in Table 2. As was observed in the simpler substrates,
Having demonstrated the effectiveness of microwave
irradiation for the coupling reaction, the functional group
tolerance of substituted aryl bromides was investigated, and
the results are summarized in Table 1. The data indicates
that the reaction is tolerant of both electron-donating (entries
1-5) and electron-withdrawing (entries 8 and 9) functional
groups.
Table 2. Coupling of Complex Aryl Bromides
In addition, it was possible to couple di-ortho-substituted
aryl bromides, demonstrating that even highly hindered
biaryls could be realized under these conditions (entry 6).
The only functional group that was found to fail in the
coupling study was the amino group, which gave starting
materials in high yield (entry 10). We attribute the failure
of this coupling reaction to poisoning of the catalyst by the
amino function. The analogous triflate coupling under
(7) (a) Wang, Y.; Sauer, D. R. Org. Lett. 2004, 6, 2793-2796. (b) Larhed,
M.; Lindeberg, G.; Hallberg, A. Tetrahedron Lett. 1996, 37, 8219-8222.
(c) Zhang, W.; Chen, C. H. T.; Lu, Y. M.; Nagashima, T. Org. Lett. 2004,
6, 1473-1476. (d) Navarro, O.; Kaur, H.; Mahjoor, P.; Nolan, S. P. J. Org.
Chem. 2004, 69, 3173-3180. (e) Leadbeater, N. E.; Marco, M. J. Org.
Chem. 2003, 68, 888-892. (f) Blettner, C. G.; Koenig, W. A.; Stenzel,
W.; Schotten, T. J. Org. Chem. 1999, 64, 3885-3890. (g) Schulz, M. J.;
Coats, S. J.; Hlasta, D. J. Org. Lett. 2004, 6, 3265-3268.
(8) Erdelyi, M.; Gogoll, A. J. Org. Chem. 2001, 66, 4165-4169.
(9) For several recent reviews, see: (a) Lidstrom, P.; Tierney, J.; Wathey,
B.; Westman, J. Tetrahedron 2001, 57, 9225-9283. (b) Perreux, L.; Loupy,
A. Tetrahedron 2001, 57, 9199-9223. (c) Lew, A.; Krutzik, P. O.; Hart,
M. E.; Chamberlin, A. R. J. Comb. Chem. 2002, 4, 95-105. (d) Larhed,
M.; Moberg, C.; Hallberg, A. Acc. Chem. Res. 2002, 35, 717-727.
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Org. Lett., Vol. 6, No. 23, 2004
Seganish, W. Michael
