Consecutive One-Pot Sonogashira-Glaser Coupling Sequence
(48), 87 (35). C20H14O4 (318.3): C 75.46, H 4.43; found C 75.22, H
4.70.
dide 1 and TMSA furnishes the TMS-protected (hetero)aryl
alkyne 3, which is deprotected with fluoride to give the cor-
responding terminal alkyne 4. Alkyne 4 (2 equiv.) now en-
ters the Glaser cycle, which is triggered by the catalytic PdII/
CuI pair. CuI ions are involved in transmetalation to PdII,
and thus a dialkynyl PdII complex is generated, which fur-
nishes the desired 1,3-butadiyne 2 upon reductive elimi-
nation. Moreover, CuI is readily oxidized to CuII by atmo-
spheric oxygen. In analogy to the Wacker oxidation,[15] an
intercepting CuI/CuII cycle fueled by oxygen is ultimately
responsible for reoxidizing Pd0 back to PdII. Interestingly,
the same mechanism that leads to the unwanted by-product
of the Sonogashira coupling in the initial activation step[16]
now becomes the modus operandi to form the desired di-
ynes 2.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and spectroscopic data for the com-
pounds prepared are presented.
Acknowledgments
The authors cordially thank Merck Serono KGaA, Darmstadt for
the financial support of this research.
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Experimental Section
Synthesis of 2m: A mixture of methyl 2-iodobenzoate (1m) (535 mg,
2.00 mmol), PdCl2(PPh3)2 (28 mg, 0.04 mmol, 2 mol-%) and CuI
(16 mg, 0.08 mmol, 4 mol-%) was dissolved in dry degassed THF
(5.00 mL) in a screw-cap Schlenk vessel with septum. After ad-
dition of TMSA (0.43 mL, 3.00 mmol) and dry triethylamine
(0.55 mL, 4.00 mmol), the solution was stirred at room temperature
(water bath) for 1 h until complete conversion (monitored by TLC).
KF (236 mg, 4.00 mmol) and methanol (5.00 mL) were then added,
and the reaction mixture was stirred in air (the reaction vessel was
opened) for 22 h. After completion of the reaction, as indicated by
TLC, the mixture was filtered and adsorbed on Celite®, and after
removal of the solvents in vacuo, the residue was purified by col-
umn chromatography on silica gel by using petroleum ether (boil-
ing range 40–60 °C)/ethyl acetate = 10:1 (Rf = 0.15) to give, after
drying in vacuo, 1,4-bis(2-methylbenzoyl)buta-1,3-diyne (2m)
(296 mg; 93%) as a yellow oil. Upon suspension in n-pentane, son-
ication in ultrasound bath, filtration and drying in vacuo, an ana-
1
lytically pure yellow solid was obtained. M.p. 59–60 °C. H NMR
(500 MHz, CDCl3): δ = 3.97 (s, 6 H), 7.40–7.44 (m, 2 H), 7.48–
7.52 (m, 2 H), 7.65–7.69 (m, 2 H), 7.97–8.00 (m, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 52.4 (CH3), 78.9 (Cquat), 81.5 (Cquat),
122.5 (Cquat), 128.8 (CH), 130.6 (CH), 131.8 (CH), 132.7 (Cquat),
135.2 (CH), 166.1 (Cquat) ppm. EI-MS (70 eV): m/z (%) = 318
[M]+ (46), 303 [M – CH3]+ (32), 285 (61), 275 (25), 272 (28), 259
[M – C2H3O2]+ (74), 258 (34), 257 (40), 204 (28), 202 [C16H10]+
(49), 200 [C16H8]+ (25), 189 (35), 188 (31), 187 (60), 176 (41), 144
(100), 133 (25), 127 (32), 114 (37), 105 (27), 101 (35), 100 (51), 88
Eur. J. Org. Chem. 2011, 238–242
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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