Copper-catalyzed coupling reaction of terminal alkynes with aryl- and alkenyliodonium salts

Article abstract of DOI:10.1021/ol0162825

(Equation presented) The copper iodide-catalyzed cross-coupling of terminal alkynes with hypervalent iodonium salts was accomplished with Cul (10 mol %) and NaHCO₃ (2 equiv) in DME/H₂O (4:1) at room temperature for 30 min to afford arylalkynes or enynes under mild conditions.

Full text of DOI:10.1021/ol0162825

ORGANIC
LETTERS
2001
Vol. 3, No. 17
2697-2699
Copper-Catalyzed Coupling Reaction of
Terminal Alkynes with Aryl- and
Alkenyliodonium Salts
Suk-Ku Kang,* Seok-Keun Yoon, and Young-Mook Kim
Department of Chemistry and BK-21 School of Molecular Science,
Sungkyunkwan UniVersity, Suwon 440-746, Korea
skkang@chem.skku.ac.kr
Received June 15, 2001
ABSTRACT
The copper iodide-catalyzed cross-coupling of terminal alkynes with hypervalent iodonium salts was accomplished with CuI (10 mol %) and
NaHCO (2 equiv) in DME/H O (4:1) at room temperature for 30 min to afford arylalkynes or enynes under mild conditions.
3
2
The palladium(0)/CuI-catalyzed cross-coupling of aryl or
vinyl halides and triflates in the presence of amine base to
form arylalkynes and conjugated enynes is known as the
Sonogashira coupling reaction1-3 and is widely utilized in
the synthesis of natural products and chemical materials.
Alternatively, the coupling reaction of aryl halide with
copper(I) acetylides in boiling pyridine, which is known as
the Castro-Stephens reaction,4 and the coupling of terminal
alkynes with vinyl halide in the presence of a stoichiometric
amount of copper species are also known.5 Recently Miura
et al.6 reported the CuI-2PPh3-catalyzed coupling of aryl or
vinyl iodide with terminal alkynes at elevated temperature
(120 °C) in DMF. The copper-catalyzed coupling of alkynes
under mild conditions is needed. In connection with our
programs to utilize iodonium salts in copper-catalyzed cross-
coupling,7 herein we wish to report CuI-catalyzed coupling
of terminal alkynes with hypervalent iodonium salts to form
arylalkynes and enynes (Scheme 1).8
Scheme 1
(1) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467-4470.
(2) Reviews: (a) Sonsgashira, K. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds; Wiley: Weinheim, 1997; Chapter
S, pp 203-229. (b) Sonogashira, K. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon: New York, 1991; Vol. 3, Chapter 2, p 4. (c)
Rossi, R.; Carpita, A.; Bellina, F. Org. Prep. Proced. Int. 1995, 27, 127-
160.
A series of experiments were performed to find an
optimum condition for the coupling of phenylacetylene (1a)
with diphenyliodonium tetrafluoroborate (2a). This cross-
(3) Recent modifications of the Sonogashira coupling: (a) Mori, A.;
Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y.
Org. Lett. 2000, 2, 2935-2937. (b) Hundertmark, T.; Littke, A. F.;
Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729-1731. (c) Nakamura,
K.; Okubo, H.; Yamaguchi, M. Synlett 1999, 549-550. (d) Nguefack, J.-
F.; Bolitt, V.; Sinou, D. Tetrahedron Lett. 1996, 37, 5527-5530. (e)
Thorand, S.; Krause, N. J. Org. Chem. 1998, 63, 8551-8553. (f) Mori, A.;
Shimada, T.; Kondn, T.; Sekiguchi, A. Synlett 2001, 649-651. (g) Bertus,
P.; Pale, P. Tetrahedron Lett. 1996, 37, 2019-2022.
(6) (a) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. Tetrahedron
Lett. 1992, 33, 5363-5364. (b) Okuro, K.; Furuune, M.; Enna, M.; Miura,
M.; Nomura, M. J. Org. Chem. 1993, 58, 4716-4721.
(7) (a) Kang, S.-K.; Yamaguchi, T.; Kim, T.-H.; Ho, P.-S. J. Org. Chem.
1996, 61, 9082-9083. (b) Kang, S.-K.; Lee, S.-H.; Lee, D. Synlett 2000,
1022-1024.
(8) The palladium-catalyzed carbonylative cross-coupling of terminal
alkynes with hypervalent iodonium salts was reported by us. (a) Kang, S.-
K.; Lee, H.-W.; Jang, S.-B.; Ho, P.-S. Chem. Commum. 1996, 835-836.
(b) Kang, S.-K.; Lim, K.-H.; Ho, P.-S.; Kim, W.-Y. Synthesis 1997, 874-
876.
(4) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313-3315.
(5) Ogawa, T.; Kusume, K.; Tanaka, M.; Hayami, K.; Suzuki, H. Synth.
Commum. 1989, 19, 2199.
10.1021/ol0162825 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/24/2001

Table 1. Cu-Catalyzed Cross-Coupling of Terminal Alkynes with Hypervalent Iodonium Salts
coupling was very sensitive to the catalysts. Of the catalysts
tested, CuI, CuCl, CuBr, CuCN, CuOAc, and CuCl2, CuI
was the best of choice. With CuCl, CuCN, CuOAc, and
CuCl2, almost no reaction occurred. As a suitable base,
NaHCO3 was the most preferred; K2CO3 and Na2CO3 gave
rather low yields. The bases Et3N, Et2NH, and NaOH were
almost ineffective. As solvent, DME/H2O (4:1) was most
suitable.
NaHCO3 (2 equiv) in DME/H2O (4:1) at room temperature
for 30 min to afford diphenylacetylene (3a)8a,9 in 85% yield
(9) A typical procedure is as follows. To a stirred solution of diphenyl-
iodonium tetrafluoroborate (2a) (1.00 g, 2.70 mmol) in DME/H2O (4:1, 10
mL) at room temperature was added NaHCO3 (499 mg, 5.94 mmol)
followed by phenylacetylene (1a) (303 mg, 2.97 mmol). The reaction
mixture was stirred for 30 min and quenched with a saturated aqueous NH4-
Cl solution (5 mL). The mixture was extracted with diethyl ether (20 mL
× 3), and the organic layer was dried over anhydrous MgSO4 and evaporated
in vacuo. The crude product was separated by SiO2 column chromatography
(hexane, Rf ) 0.48) to give diphenylacetylene (3a)8a (409 mg, 85%): 1H
NMR (500 MHz, CDCl3) δ ) 7.54 (m, 6H), 7.54 (m, 4H); IR (KBr) ν )
3063, 1560, 1500, 1070, 918 cm-1; MS (m/e) ) 178 (M+, base peak), 152,
89, 88, 76.
The results of the CuI-catalyzed cross-coupling reaction
of terminal alkynes with aryl- and alkenyliodonium salts are
summarized in Table 1. The phenylacetylene (1a) reacted
-
with Ph2I+ BF4 in the presence of CuI (10 mol %) and
2698
Org. Lett., Vol. 3, No. 17, 2001

(entry 1 in Table 1). It is notable that no homo-coupling
products were detected under these conditions. Under the
same conditions, p-methoxyphenyl(phenyl)iodonium salt 2b
as electrophile, p-methoxyphenyl transferred product 3b10
was afforded as the sole product (entry 2). This method was
applied to alkenyl-substituted iodonium salt 2d, and the
coupled enyne 3d8a was obtained in 70% yield (entry 4).
1-Hexyne 1b and propargyl alcohol 1c were utilized in this
coupling method. 1-Hexyne (1b) was treated with iodonium
salts 2a and 2c to afford the coupling products 3e8a and 3f8a
(entries 5 and 6). The substituted propargyl alcohols 1c and
1d were also used in the copper-catalyzed cross-coupling
(entries 8-13). This copper-catalyzed cross-coupling method
was extended to electron-deficient alkynes. Ethyl propiolate
was reacted with iodonium salts 2a and 2c to afford the aryl-
substituted propiolates 3n11 and 3o12 in 68 and 62% yields,
respectively (entries 14 and 15).11
Table 2. One-Pot Direct Cross-Coupling of Acetylenic Alcohol
with Hypervalent Iodonium Salts in the Presence of CuI under
Basic Conditions
entry
substrate
iodonium salt
product
yield (%)
1
2
3
4
5
6
7
3j
3j
3j
3j
3k
3l
3m
2a
2b
2c
2d
2a
2a
2a
3a
2b
3c
3d
3b
3c
3d
80
70
62
63
66
60
56
p-methoxyphenyl(phenyl)iodonium salt 2b in the presence
of CuI (10 mol %) with NaOH and 1-butanol at reflux for
24 h to afford the disubstituted acetylene 3b in 70% yield
(entry 1 in Table 2). Under the same conditions, the
acetylenic alcohol 3j was treated with iodonium salts 2c and
2d to provide 3c8a and 3d (entries 2 and 3). Alternatively,
the acetylenic alcohols 3k-3m were readily deprotected and
coupled in a one-pot procedure under the same conditions
to give 3b, 3c, and 3d in moderate yields (entries 4-6).
In summary, we have developed a new and mild protocol
for Sonogashira coupling with CuI as catalyst utilizing
hypervalent iodonium salts as the electrophilic coupling
partners and multiple Sonogashira reactions for the synthesis
of disubstituted acetylenes.
Next we investigated the one-pot and direct coupling of
the acetylenic alcohols 3j-3m with hypervalent iodonium
salts in the presence of copper catalyst CuI under basic
conditions. Indeed, acetylenic alcohols 3j-3m can be
transformed into arylethynes under these conditions (Scheme
2).18,19
Scheme 2
Acknowledgment. This work is supported by a National
Research Laboratory Grant by the Korea Ministry of Science
and Technology and KOSEF-CMDS (Center for Molecular
Design and Synthesis).
OL0162825
The results of the direct and one-pot cross-coupling of
acetylenic alcohol 3 with hypervalent iodonium salts 2 under
copper catalysis to form disubstituted acetylenes are sum-
marized in Table 2. The acetylenic alcohol 3j reacted with
NMR (500 MHz, CDCl3) δ 1.35 (t, 3H, J ) 7 Hz), 4.30 (q, 2H, J ) 7 Hz)
7.37 (m, 2H), 7.44 (m, 1H), 7.58 (m, 2h); IR (neat) ν ) 3083, 3038, 2985,
2210, 1715, 1491, 1368, 1240 cm-1; ΗRMS calcd for C11H10O2 174.0681,
found 174.0680. 3o: 1H NMR (500 MHz, CDCl3) δ 1.35 (t, 3H, J ) 7 Hz),
4.30 (q, 2H, J ) 7 Hz) 7.05 (m, 1H), 7.47 (m, 2H); IR (neat) ν ) 3091,
2989, 2214, 2129, 1769, 1665, 1584, 1470, 1370, 1271 cm-1; ΗRMS calcd
for C9H8O2S 180.0245, found 180.0245.
(15) Berigbreite, D. E.; Liu, Y. S. Tetrahedron Lett. 1992, 38, 7843-
7846.
(16) Mal’kina, A. G.; Brandsma, L.; Vasilevsky, B. A.; Trofima, B. A.
Synthesis 1996, 589-590.
(17) Ooi. T.; Miura, T.; Maruoka, K. J. Am. Chem. Soc. 1998, 120,
10790-10791.
(10) Kang, S.-K.; Baik, T.-G.; Song, S.-Y. Synlett 1999, 327-329.
(11) Recently Stang et al. reported the palladium-catalyzed arylation of
electron-deficient alkynes using diaryliodonium salts. See: Radhakrishnan,
U.; Stang, P. J. Org. Lett. 2001, 3, 859-860.
(12) Brittain, J. M.; Jones, A.; Taheri, A. N. Tetrahedron 1980, 36, 7609-
7618.
(13) Hurley, A. L.; Welker, M. E.; Day, C. S. J. Organomet. Chem.
2000, 150-159.
(14) The spectral and physical data of 3h, 3j, 3k, 3l, 3m, 3n and 3o. 3h:
1H NMR (500 MHz, CDCl3) δ 1.63 (t, 1H, J ) 6 Hz), 3.81 (s, 3H), 4.49
(d, 2H, J ) 6 Hz), 6.84 (dd, 2H, J ) 6.5, 2 Hz), 7.38 (dd, 2H, J ) 6.5, 2
Hz); IR (KBr) ν ) 3250, 2963, 2233, 1603, 1509, 1291, 1253 cm-1; ΗRMS
calcd for C10H10O2 162.0681, found 162.0682. 3j: 1H NMR (500 MHz,
CDCl3) δ 1.62 (s, 6H), 7.28 (m, 3H), 7.41 (m, 2H); IR (KBr) ν ) 3395,
3058, 2983, 2232, 1953, 1881, 1598, 1490 cm-1; ΗRMS calcd for C11H12O
160.0888, found 160.0889. 3k: 1H NMR (500 MHz, CDCl3) δ 1.61 (s,
6H), 3.80 (s 3H), 6.82 (d, 2H J ) 9 Hz), 7.35 (d, 2H J ) 9 Hz); IR (KBr)
ν ) 3378, 3043, 2981, 2839, 2228, 1607, 1510, 1463, 1249 cm-1; ΗRMS
calcd for C12H14O2 190.0994, found 190.0994. 3l: 1H NMR (500 MHz,
CDCl3) δ 1.61 (s, 6H), 6.94 (m, 1H), 7.17 (m, 1H), 7.22 (m, 1H); IR (KBr)
ν ) 3357, 3108, 2983, 2222, 1518, 1452, 1261 cm-1; ΗRMS calcd for
(18) The direct cross-coupling between acetylenic alcohols and aryl halide
under basic conditions with Pd(0)/CuI catalysts is known. See: Chow, H.-
F.; Wan, C.-W.; Low, K.-H.; Yeung, Y.-Y. J. Org. Chem. 2001, 66, 1910-
1913.
(19) Typical procedure is as follows. To stirred solution of 2-methyl-4-
phenyl-3-butyn-2-ol (3j) (1.00 g, 6.24 mmol), 4-methoxyphenyl(phenyl)-
iodonium tetrafluoroborate (2b) (2.49 g, 6.24 mmol), and CuI (0.12 g, 0.63
mmol) in butanol (10 mL) was added NaOH (2.00 g, 49.92 mmol). The
reaction mixture was heated at reflux for 24 h and then quenched with a
saturated aqueous NH4Cl solution (5 mL). The reaction mixture was
extracted with diethyl ether (20 mL × 3), and the organic layer was dried
over anhydrous MgSO4 and evaporated in vacuo. The crude product was
separated by SiO2 column chromatography (EtOAc/hexane ) 1:10, Rf )
0.52) to give 1-methoxy-4-(phenylethynyl)benzene (3b) (910 mg, 70%):
1H NMR (500 MHz, CDCl3) δ ) 3.83 (s, 3H), 6.88 (d, 2H, J ) 8.5 Hz),
1
C9H10OS 166.0452, found 166.0453. 3m: H NMR (500 MHz, CDCl3) δ
1.62 (s, 6H), 6.16 (d, 1H, J ) 16.5 Hz), 6.93 (d, 1H, J ) 16.5 Hz), 7.35
(m, 5H); IR (KBr) ν ) 3356, 3029, 2981, 2213, 1491, 1448, 1366, 1164,
953 cm-1; ΗRMS calcd for C13H14O 186.1045, found 186.1048. 3n: 1H
7.29 (m, 3H), 7.49 (m, 4H); IR (KBr) ν ) 3080, 2958, 1617, 1405 cm-1
MS (m/e) ) 208 (M+), 207 (base peak), 193, 165.
;
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