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J. Wettergren, A. B. E. Minidis / Tetrahedron Letters 44 (2003) 7611–7612
Table 1. Methoxylation of aryl alkynes
Substrate
1:2:3 at rta
1:2:3 at refluxb
1:2:3 in a microwave ovenc
R=H, Ar=4-MeO-Ph
R=TMS, Ar=Ph
R=TMS, Ar=3-Pyridyl
R=TMS, Ar=2-Pyridyl
R=TMS, Ar=2-NC-Ph
R=TMS, Ar=4-O2N-Ph
No reaction
100:0:0
100:0:0
100:0:0
100:0:0
No reaction
100:0:0
N.d. (55% 2 (72 h), Ref. 2)
N.d. (60% 2 (5 h), Ref. 2)
75:20:5
No reaction
100:0:0
75:25:0
6:94:0
9:82:9
100:0:0
0:0:100 (72 h)d
23:35:42 (24 h)
40:60:0
N.d.
100:0:0
0:2:98f
R=TMS, Ar=2-O2N-Ph
R=TMS, Ar=2-Quinoxalyl
R=TMS, Ar=2-Cl-Ph
R=TMS, Ar=3-Br-Ph
R=TMS, Ar=4-Br-Ph
100:0:0
0:0:100e
N.d.
N.d.
N.d.
0:8:92f
0:03:97f
56:8:36g
91:9:0g
100:0:0
100:0:0
86:14:0g
a
10 equiv. K2CO3, MeOH, rt, 24 h.
b 10 equiv. K2CO3, MeOH, reflux, 24 h.
c
10 equiv. K2CO3, MeOH, 120–130°C, 15 min, microwave irradiation.10 Ratios given are proton NMR integral ratios.
Quantitative isolated yield.
d
e 92% isolated.
f Combined isolated yield: quant.
g
Ratios given are non standardized CI-GC/MS ratios. Note that in EI-GC/MS the diacetals in some cases only show M+−31 (i.e. M+−MeO),
which can be mistaken for the mono-adduct.
Acknowledgements
Organic Chemistry, 3rd ed.; Wiley-Interscience: New
York, 1999; Chapter 8, pp. 654–659.
7. See e.g.: (a) Sonogashira, K.; Tohda, Y.; Hagihara, N.
Tetrahedron Lett. 1975, 16, 4467–4470; (b) Lee, J.-H.;
Park, J.-S.; Cho, C.-G. Org. Lett. 2002, 4, 1171–1173.
8. This is in stark contrast to Dinsmore, A.; Birks, J. H.;
Garner, C. D.; Joule, J. A. J. Chem. Soc., Perkin Trans.
1 1997, 801–807. The authors report a high yield for
2-ethynylquinoxaline after 19 h in K2CO3/MeOH.
9. Higher temperatures can be achieved by the addition of a
few drops of DMF. (Anders Franze´n, Personal Chem-
istry, Sweden, personal communication). Under such con-
ditions conversions slow down and the reactions proceed
less cleanly.
We thank AstraZeneca for supporting this work, Dr.
D. Wensbo and Dr. J.-E. Lindgren for helpful discus-
sions and Allen Farrokhi for experimental support.
References
1. For selected examples, see: (a) Reichert, J. S.; Bailey, J.
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10. Microwave reactions were run in 5 mL heavy-walled glass
Smith process vials sealed with aluminum crimp caps
fitted with a silicone septum. The oven was a Smith
Synthesizer Single-mode microwave cavity producing
continuous irraditation at 2450 MHz (Personal Chem-
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dure: 0.6 mmol of aryl (trimethylsilyl)ethyne and 6.0
mmol of potassium carbonate were mixed in 5 mL
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or 130°C for 15 min. Work-up was performed by adding
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